Welcome to our monthly trawl for developmental biology (and other related) preprints!

This month we found a tranche of preprints getting deep into the mechanics of fly development, a clutch on organoids (retinal, cerebral, cortical!), an investigation into the role of gender in scientific collaboration, and a veritable zoo in our evo-devo section – from ladybirds to placozoans via pufferfish, hydra and choanoflagellates.

The preprints were hosted on bioRxiv, PeerJ, and arXiv. Let us know if we missed anything, and use these links to get to the section you want:

Developmental biology

| Patterning & signalling

| Morphogenesis & mechanics

| Genes & genomes

| Stem cells, regeneration & disease modelling

Evo-devo & evo

Cell biology

Modelling

Tools & resources

| Imaging etc.

| Genome tools

Research practice & education

Why not…

Developmental biology

| Patterning & signalling

Canonical Wnt signaling regulates patterning, differentiation and nucleogenesis in mouse hypothalamus and prethalamus.
Elizabeth Newman, Dan Wu, Makoto Mark Taketo, Jiangyang Zhang, Seth Blackshaw

Dll1 and Jag1 are Differentially Required to Specify Proximal and Distal Pancreatic Duct Compartments
Philip A Seymour, Caitlin A Collin, Mette C Jorgensen, Itaru Imayoshi, Ryoichiro Kageyama, Palle Serup

Notch Controls Multiple Pancreatic Cell Fate Regulators Through Direct Hes1-mediated Repression
Kristian H de Lichtenberg, Philip A Seymour, Mette C Jorgensen, Yung-Hae Kim, Anne Grapin-Botton, Mark Magnuson, Nikolina Nakic, Jorge Ferrer, Palle Serup

Gain-of-function Shh mutants activate Smo in cis independent of Ptch1/2 function
Catalina Casillas, Henk Roelink

Sonic Hedgehog is a member of the Hh/DD-peptidase family that spans the eukaryotic and bacterial domains of life.
Henk Roelink

The chemokine receptor CXCR2 contributes to murine adipocyte development
Douglas P Dyer, Joan Boix Nebot, Christopher Kelly, Laura Medina-Ruiz, Fabian Scheutte, Gerard J Graham

Thyroid hormone signaling specifies cone subtypes in human retinal organoids
Kiara C Eldred, Sarah E Hadyniak, Katarzyna A Hussey, Boris Brennerman, Pingwu Zhang, Xitiz Chamling, Valentin M Sluch, Derek S Welsbie, Samer Hattar, James Taylor, Karl Wahlin, Donald J Zack, Robert J Johnston Jr.

Lineage segregation, pluripotency and X-chromosome inactivation in the pig pre-gastrulation embryo
Priscila Ramos-Ibeas, Fei Sang, Qifan Zhu, Walfred W.C. Tang, Sarah Withey, Doris Klisch, Matthew Loose, Azim Surani, Ramiro Alberio

Chronic estrus disrupts uterine gland development and homeostasis
C. Allison Stewart, M. David Stewart, Ying Wang, Rui Liang, Yu Liu, Richard Behringer

Amot regulates neuronal dendritic tree through Yap1
Katarzyna O. Rojek, Joanna Krzemien, Hubert Dolezyczek, Pawel M. Boguszewski, Leszek Kaczmarek, Witold Konopka, Marcin Rylski, Jacek Jaworski, Lars Holmgren, Tomasz J. Proszynski

Single-cell ID-seq identifies BMP signaling as a driver of a late stage epidermal differentiation program.
Roderick E. van Eijl, Jessie A.G. van Buggenum, Sabine E.J. Tanis, Joost Hendriks, Klaas W. Mulder

Feedback Regulation between Initiation and Maturation Networks Orchestrates the Chromatin Dynamics of Epidermal Lineage Commitment
Lingjie Li, Yong Wang, Jessica L. Torkelson, Gautam Shankar, Jillian M. Pattison, Hanson H. Zhen, Zhana Duren, Fengqin Fang, Sandra P. Melo, Samantha N. Piekos, Jiang Li, Eric J. Liaw, Lang Chen, Rui Li, Marius Wernig, Wing H. Wong, Howard Y. Chang, Anthony E. Oro

Morphogen-Lineage Selector Interactions During Surface Epithelial Commitment
Sandra P Melo, Jillian M Pattison, Samantha N Piekos, Jessica L Torkelson, Elizaveta Bashkirova, Maxwell R Mumbach, Charlotte Rajasingh, Hanson Hui Zhen, Lingjie Li, Eric Liaw, Daniel Alber, Adam J Rubin, Gautam Shankar, Howard Y Chang, Paul A Khavari, Anthony E Oro

Single cell expression analysis uncouples transdifferentiation and reprogramming
Mirko Francesconi, Bruno Di Stefano, Clara Berenguer, Marisa de Andres, Maria Mendez Lago, Amy Guillaumet-Adkins, Gustavo Rodriguez-Esteban, Marta Gut, Ivo Gut, Holger Heyn, Ben Lehner, Thomas Graf

Rainbow-seq: combining cell lineage tracking with single-cell RNA sequencing in preimplantation embryos
Fernando Biase, Qiuyang Wu, Riccardo Calandrelli, Marcelo Rivas-Astroza, Shuigeng Zhou, Sheng Zhong

Paralogues of the PXY and ER receptor kinases enforce radial patterning in plant vascular tissue.
Ning Wang, Kristine S Bagdassarian, Rebecca Doherty, Xiao Wang, Johannes Kroon, Wei Wang, Ian Jermyn, Simon Turner, Peter Etchells

β-cyclocitral is a natural root growth regulator
Alexandra J Dickinson, Kevin Lehner, Medhavinee Mijar, Philip N Benfey

TTL proteins scaffold brassinosteroid signaling components at the plasma membrane to optimize signal transduction in plant cells
Vitor Amorim-Silva, Alvaro Garcia-Moreno, Araceli G Castillo, Naoufal Lakhssassi, Jessica Perez-Sancho, Yansha Li, Alicia Esteban del Valle, David Pose, Josefa Perez-Rodriguez, Jinxing Lin, Victoriano Valpuesta, Omar Borsani, Cyril Zipfel, Alberto P Macho, Miguel A Botella

Drosophila IMP regulates Kuzbanian to control the timing of Notch signalling in the follicle cells
Weronicka Fic, Celia Faria, Daniel St Johnston

Distinct roles and requirements for Ras pathway signaling in visceral versus somatic muscle founder specification
Yiyun Zhou, Sarah E. Popadowski, Emily Deustchman, Marc S. Halfon

A repressor-decay timer for robust temporal patterning in embryonic Drosophila neuroblast lineages
Inna Averbukh, Sen-Lin Lai, Chris Q Doe, Naama Barkai

Altered hsrω lncRNA levels in activated Ras background further enhance Ras activity in Drosophila eye and induces more R7 photoreceptors
Mukulika Ray, Subhash C. Lakhotia

Signaling dynamics control cell fate in the early Drosophila embryo
Heath E Johnson, Stanislav Y Shvartsman, Jared E Toettcher

Kinetic sculpting of the seven stripes of the Drosophila even-skipped gene
Augusto Berrocal, Nicholas C Lammers, Hernan G Garcia, Michael B Eisen

A fat-tissue sensor couples growth to oxygen availability by remotely controlling insulin secretion
Michael J. Texada, Anne F. Joergensen, Daniel K. Smith, Dylan F.M. Marple, E. Thomas Danielsen, Sine K. Petersen, Jakob L. Hansen, Kenneth A. Halberg, Kim F. Rewitz

TORC1 modulation in adipose tissue is required for organismal adaptation to hypoxia in Drosophila.
Byoungchun Lee, Elizabeth C Barretto, Savraj S Grewal

Phosphatidylinositol 5 phosphate 4-kinase regulates insulin sensitivity and PIP3 turnover in Drosophila.
Sanjeev Sharma, Swarna Mathre, Ramya Visvanathan, Dhananjay Shinde, Padinjat Raghu

Glucose increases the lifespan of post-reproductive C. elegans independently of FOXO
Lei Wang, Caroline Beaudoin-Chabot, Guillaume Thibault

Perception of environmental polypeptides in C. elegans activates insulin/IGF signaling and alters lipid metabolism
Rebecca E. W. Kaplan, Amy K. Webster, Rojin Chitrakar, Joseph A. Dent, L. Ryan Baugh

A functional study of all 40 C. elegans insulin-like peptides
Shanqing Zheng, Hilton Chiu, Jeffrey Boudreau, Tony Papanicolaou, William Bendena, Ian Chin-Sang

Intergenerational effects of dietary restriction on insulin/IGF signaling and reproductive development
James M. Jordan, Jonathan D. Hibshman, Rebecca E. W. Kaplan, Amy K. Webster, Abigail Leinroth, Ryan Guzman, Colin S. Maxwell, Elizabeth Anne Bowman, E. Jane Albert Hubbard, L. Ryan Baugh

Variability in the timing of a β-catenin pulse biases a stochastic cell fate decision in C. elegans
Jason R Kroll, Jasonas Tsiaxiras, Jeroen S van Zon

| Morphogenesis & mechanics

Mechanosensitive binding of p120-Catenin at cell junctions regulates E-Cadherin turnover and epithelial viscoelasticity
K. Venkatesan Iyer, Romina Piscitello-Gómez, Frank Jülicher, Suzanne Eaton

Analysis of the role of Nidogen/entactin in basement membrane assembly and morphogenesis in Drosophila
Maria Dolores Martin-Bermudo, Jianli Dai, Beatriz Estrada, Sofie Jacobs, Besaiz Sánchez-Sánchez, Jia Tang, Mengqi Ma, Patricia Magadan, José C. Pastor-Pareja

Characterization of Drosophila Nidogen/entactin reveals roles in basement membrane stability, barrier function and nervous system plasticity
Georg Wolfstetter, Ina Dahlitz, Kathrin Pfeifer, Joscha Arne Alt, Uwe Toepfer, Daniel Christoph Pfeifer, Reinhard Lakes-Harlan, Stefan Baumgartner, Ruth Palmer, Anne Holz

Dynamics of PAR proteins explain the oscillation and ratcheting mechanisms in dorsal closure
Clinton H. Durney, Tony J. C. Harris, James J. Feng

A Fasciclin 2 functional switch controls organ size in Drosophila
Emma Velasquez, Jose Gomez-Sanchez, Emmanuelle Donier, Carmen Grijota-Martinez, Hugo Cabedo, Luis A Garcia-Alonso

Targeted substrate degradation by Kelch controls the actin cytoskeleton during ring canal expansion
Andrew M. Hudson, Katelynn M. Mannix, Julianne A. Gerdes, Molly C. Kottemann, Lynn Cooley

TIAM-1/GEF can shape somatosensory dendrites independently of its GEF activity by regulating F-actin localization
Leo T.H. Tang, Carlos A Diaz-Balzac, Maisha Rahman, Nelson J Ramirez-Suarez, Yehuda Salzberg, Maria I Lazaro-Pena, Hannes E Bülow

Distinct CED-10/Rac1 Domains Confer Context-Specific Functions in Neuronal Development
Roger Pocock, Steffen Noergaard, Shuer Deng, Wei Cao

Novel exc Genes Involved in Formation of the Tubular Excretory Canals of C. elegans
Hikmat Al-Hashimi, Travis Chiarelli, Erik A. Lundquist, Matthew Buechner

Size control of the inner ear via hydraulic feedback
Kishore R. Mosaliganti, Ian A. Swinburne, Chon U Chan, Nikolaus D. Obholzer, Amelia A. Green, Shreyas Tanksale, L Mahadevan, Sean G. Megason

N-Cadherin Provides a Cis and Trans Ligand for Astrotactin that Functions in Glial-Guided Neuronal Migration
Zachi Horn, Hourinaz Behesti, Mary E. Hatten

Actomyosin dynamics, Bmp and Notch signaling pathways drive apical extrusion of proepicardial cells
Laura Andres-Delgado, Alexander Ernst, Maria Galardi-Castilla, David Bazaga, Marina Peralta Lopez, Juliane Munch, Juan Manuel Gonzalez-Rosa, Federico Tessadori, Jeroen Bakkers, Jose Luis De La Pompa Minguez, Julien Vermot, Nadia Mercader

Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output
Stefano L Giandomenico, Susanna B Mierau, George M Gibbons, Lea MD Wenger, Laura Masullo, Timothy Sit, Magdalena Sutcliffe, Jerome Boulanger, Marco Tripodi, Emmanuel Derivery, Ole Paulsen, Andras Lakatos, Madeline Lancaster

Nested oscillatory dynamics in cortical organoids model early human brain network development
Cleber A. Trujillo, Richard Gao, Priscilla D. Negraes, Isaac A. Chaim, Alain Domissy, Matthieu Vandenberghe, Anna Devor, Gene W. Yeo, Bradley Voytek, Alysson R. Muotri

Cerebellar nuclei neurons dictate growth of the cortex through developmental scaling of presynaptic Purkinje cells
Ryan T Willett, Alexandre Wojcinski, Nermin Sumru Bayin, Zhimin Lao, Daniel Stephen, Katherine L Dauber-Decker, Zhuhao Wu, Marc Tessier-Lavigne, Hiromitsu Saito, Noboru Suzuki, Alexandra L Joyner

Three-dimensional organization of transzonal projections and other cytoplasmic extensions in mouse ovarian follicles
Valentina Baena, Mark Terasaki

Active fluctuations modulate gene expression in mouse oocytes
Maria Almonacid, Stephany El-Hayek, Alice Othmani, Isabelle Queguiner, Fanny Coulpier, Sophie Lemoine, Leïla Bastianelli, Christophe Klein, Tristan Piolot, Philippe Mailly, Raphaël Voituriez, Auguste Genovesio, Marie-Hélène Verlhac

Zebrafish hhex null mutant develops an intrahepatic intestinal tube due to de-repression of cdx1b and pdx1
Ce Gao, Weidong Huang, Yuqi Gao, Li Jan Lo, Lingfei Luo, Honghui Huang, Jun Chen, Jinrong Peng

A novel mechanism of gland formation in zebrafish involving transdifferentiation of renal epithelial cells and live cell extrusion
Richard W Naylor, Alan J Davidson

Linear stability analysis of morphodynamics during tissue regeneration in plants
Anne-Mieke Reijne, Gunnar Pruessner, Giovanni Sena

Light dynamically regulates growth rate and cellular organisation of the Arabidopsis root meristem.
Thomas Blein, Jasmin Duerr, Taras Pasternak, Thomas Haser, Thorsten Falk, Kun Liu, Franck Anicet Ditengou, Olaf Ronneberger, Klaus Palme

Cellular heterogeneity in pressure and growth emerges from tissue topology and geometry
Yuchen Long, Ibrahim Cheddadi, Vincent Mirabet, Mathilde Dumond, Christophe Godin, Arezki Boudaoud

| Genes & genomes

Pou5f3, SoxB1 and Nanog remodel chromatin on High Nucleosome Affinity Regions at Zygotic Genome Activation
Marina Veil, Lev Yampolsky, Bjoern Gruening, Daria Onichtchouk

Nucleoporin 133 deficiency leads to glomerular damage in zebrafish
Chiara Cianciolo Cosentino, Alessandro Berto, Michelle Hari, Johannes Loffing, Stephan C. F. Neuhauss, Valerie Doye

Myc is dispensable for cardiac development in the mouse but can rescue Mycn-deficient hearts through functional replacement and cell competition
Noelia Muñoz-Martín, Rocío Sierra, Thomas Schimmang, Cristina Villa del Campo, Miguel Torres

Timed collinear activation of Hox genes during gastrulation controls the avian forelimb position
Chloe Moreau, Paolo Caldarelli, Didier Rocancourt, Julian Roussel, Nicolas Denans, Olivier Pourquie, Jerome Gros

Tbx1 represses Mef2c gene expression by inducing histone 3 deacetylation of the anterior heart field enhancer
Luna Simona Pane, Filomena Gabriella Fulcoli, Andrea Cirino, Alessandra Altomonte, Rosa Ferrentino, Marchesa Bilio, Antonio Baldini

DNMT1 in Six2 progenitor cells is essential for transposable element silencing and kidney development
Szu-Yuan Li, Jihwan Park, Kiwung Chung, Rojesh Shrestha, Matthew B Palmer, Katalin Susztak

Using human sequencing to guide craniofacial research.
Ryan Liegel, Erin Finnerty, Lauren Ward, Andrew DiStasio, Robert Hufnagel, Howard Saal, Cynthia Prows, Rolf Stottmann, Rolf Stottmann

Spatiotemporal Gene Coexpression and Regulation in Mouse Cardiomyocytes of Early Cardiac Morphogenesis
Yang Liu, Pengfei Lu, Yidong Wang, Bernice E. Morrow, Bin Zhou, Deyou Zheng

Genome-wide analysis of H3K4me3 and H3K27me3 modifications throughout the mouse urogenital ridge at E11.5.
Yisheng Yang, Megan J Wilson

Mutations in Kinesin Family Member 6 Reveal Specific Role in Ependymal Cell Function and Human Neuro-Cranial Development
Mia J Konjikusic, Patra Yeetong, Rungnapa Ittiwut, Kanya Suphapeetiporn, John B Wallingford, Christina A Gurnett, Vorasuk Shotelersuk, Ryan Gray

Cardiac differentiation at single cell resolution reveals a requirement of hypertrophic signaling for HOPX transcription
Clayton Friedman, Quan Nguyen, Samuel Lukowski, Abbigail Helfer, Han Chiu, Holly Voges, Shengbao Suo, Jing-Dong Han, Pierre Osteil, Guangdun Peng, Naihe Jing, Greg Ballie, Anne Senabouth, Angelika Christ, Timothy Bruxner, Charles Murry, Emily Wong, Jun Ding, Yuliang Wang, James Hudson, Ziv Bar-Joseph, Patrick Tam, Joseph Powell, Nathan Palpant

Staged developmental mapping and X chromosome transcriptional dynamics during mouse spermatogenesis
Christina Ernst, Nils Eling, Celia P. Martinez-Jimenez, John C. Marioni, Duncan T. Odom

Altering the temporal regulation of one transcription factor drives sensory trade-offs
Ariane Ramaekers, Simon Weinberger, Annelies Claeys, Martin Kapun, Jiekun Yan, Reinhard Wolf, Thomas Flatt, Erich Buchner, Bassem A Hassan

The BTB-ZF transcription factor Tramtrack 69 shapes neural cell lineages by coordinating cell proliferation and cell fate
Francoise Simon, Anne Ramat, Sophie Louvet-Vallee, Angelique Burg, Agnes Audibert, Michel Gho

Drosophila small ovary encodes a zinc-finger repressor required for ovarian differentiation
Leif Benner, Elias A Castro, Cale Whitworth, Koen JT Venken, Haiwang Yang, Brian Oliver, Dorothy Lerit, Kevin R Cook

The mirtron miR-1010 functions in concert with its host gene SKIP to maintain synaptic homeostasis
Christopher Amourda, Timothy E Saunders

Contrasting effects of aging on the expression of transposons, the piRNA machinery and mitochondrial transcripts in the Drosophila ovary.
Alexandra A. Erwin, Justin P. Blumenstiel

Gene-regulatory independent functions for insect DNA methylation
Adam J. Bewick, Zachary Sanchez, Elizabeth C. Mckinney, Allen J. Moore, Patricia J. Moore, Robert J. Schmitz

Chromatin accessibility is dynamically regulated across C. elegans development and ageing
Jurgen Janes, Yan Dong, Michael Schoof, Jacques Serizay, Alex Appert, Chiara Cerrato, Carson Woodbury, Ron Chen, Carolina Gemma, Ni Huang, Djem Kissiov, Przemyslaw Stempor, Annette Steward, Eva Zeiser, Sascha Sauer, Julie Ahringer

Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in C. elegans embryos
Beste Mutlu, Huei-Mei Chen, James J. Moresco, Barbara D. Orelo, Bing Yang, John M. Gaspar, Sabine Keppler-Ross, John R. Yates III, David H. Hall, Eleanor M. Maine, Susan E. Mango

ZAG-1/ZEB prevents the expression of repressors and protects neuronal cell fate in Caenorhabditis elegans
Chaogu Zheng, Felix Qiaochu Jin, Brian Loeber Trippe, Ji Wu, Martin Chalfie

H3K9me3 is Required for Transgenerational Inheritance of Small RNAs that Target a Unique Subset of Newly Evolved Genes
Itamar Lev, Hila Gingold, Oded Rechavi

Dauer diapause has transgenerational effects on starvation survival and gene expression plasticity
Amy K Webster, James M Jordan, Jonathan D Hibshman, Rojin Chitrakar, L Ryan Baugh

Spatial transcriptomics of C. elegans males and hermaphrodites identifies novel fertility genes
Annabel Ebbing, Abel Vertesy, Marco Betist, Bastiaan Spanjaard, Jan Philipp Junker, Alexander van Oudenaarden, Eugene Berezikov, Hendrik Korswagen

A variably imprinted epiallele impacts seed development
Daniela Pignatta, Katherine Novitzky, P.R. V. Satyaki, Mary Gehring

Developmental genetics of corolla tube formation: role of the tasiRNA-ARF pathway
Baoqing Ding, Rui Xia, Qiaoshan Lin, Vandana Gurung, Janelle M. Sagawa, Lauren E. Stanley, Matthew Strobel, Pamela K. Diggle, Blake C. Meyers, Yao-Wu Yuan

Distinct types of short open reading frames are translated in plant cells
Igor Fesenko, Ilya Kirov, Andrey Kniazev, Regina Khazigaleeva, Vassili Lazarev, Daria Kharlampieva, Ekaterina Grafskaia, Viktor Zgoda, Ivan Butenko, Georgy Arapidi, Anna Mamaeva, Vadim Ivanov, Vadim Govorun

Functional Analysis of TM6 MADS box gene in the Octoploid Strawberry by CRISPR/Cas9 directed mutagenesis
Carmen Martín-Pizarro, Juan Carlos Triviño, David Posé

Exploration of miRNA-mediated fertility regulation network of cytoplasmic male sterility during flower bud development in soybean
Xianlong Ding, Hao Zhang, Hui Ruan, Yanwei Li, Linfeng Chen, Tanliu Wang, Ling Jin, Xiaoqiang Li, Shouping Yang, Junyi Gai

A Genome-Wide Association Study Reveals a Novel Regulator of Ovule Number and Fertility in Arabidopsis thaliana
Jing Yuan, Sharon A Kessler

| Stem cells, regeneration & disease modelling

Conservation of epigenetic regulation by the MLL3/4 tumour suppressor in planarian pluripotent stem cells
Yuliana Mihaylova, Prasad Abnave, Damian Kao, Samantha Hughes, Alvina Lai, Farah Jaber-Hijazi, Nobuyoshi Kosaka, Aziz Aboobaker

Hair Follicle Epidermal Stem Cells Define a Niche for Tactile Sensation
Chun-Chun Cheng, Ko Tsutsui, Toru Taguchi, Noriko Sanzen, Asako Nakagawa, Kisa Kakiguchi, Shigenobu Yonemura, Chiharu Tanegashima, Sean D Keeley, Hiroshi Kiyonari, Yasuhide Furuta, Yasuko Tomono, Fiona M. Watt, Hironobu Fujiwara

“Ancestralization” of human pluripotent stem cells by multiplexed precise genome editing
Stephan Riesenberg, Tomislav Maricic, Svante Pääbo

A common molecular logic determines embryonic stem cell self-renewal and reprogramming
Sara-Jane Dunn, Meng Amy Li, Elena Carbognin, Austin G Smith, Graziano Martello

Single-cell transcriptomics identifies CD44 as a new marker and regulator of haematopoietic stem cells development
Morgan Oatley, Ozge Vargel Bolukbasi, Valentine Svensson, Maya Shvartsman, Kerstin Ganter, Katharina Zirngibl, Polina V Pavlovich, Vladislava Milchevskaya, Vladimira Foteva, Kedar N. Natarajan, Bianka Baying, Vladimir Benes, Kiran Raosaheb Patil, Sarah A. Teichmann, Christophe Lancrin

LncRNA Spehd regulates hematopoietic stem cells and progenitors and is required for multilineage differentiation
M Joaquina Delás, Benjamin T Jackson, Tatjana Kovacevic, Silvia Vangelisti, Ester Munera Maravilla, Sophia A Wild, Eva Maria Stork, Nicolas Erard, Simon RV Knott, Gregory J Hannon

O-GlcNAc Homeostasis Controls Cell Fate Decisions During Hematopoiesis
Zhen Zhang, Matt P Parker, Stefan Graw, Lesya Novikova, Halyna Fedosyuk, Joseph Fontes, Devin Koestler, Kenneth Peterson, Chad Slawson

Histone Acetyltransferase Kat2a Stabilises Pluripotency with Control of Transcriptional Heterogeneity
Naomi Moris, Shlomit Edri, Denis Seyres, Rashmi Kulkarni, Ana Filipa Domingues, Tina Balayo, Mattia Frontini, Cristina Pina

Profiling of pluripotency factors in individual stem cells and early embryos
Sarah J Hainer, Ana Boskovic, Oliver J Rando, Thomas G Fazzio

Genome-scale oscillations in DNA methylation during exit from pluripotency
Steffen Rulands, Heather J Lee, Stephen J Clark, Christof Angermueller, Sebastien A Smallwood, Felix Krueger, Hisham Mohammed, Wendy Dean, Jennifer Nichols, Peter Rugg-Gunn, Gavin Kelsey, Oliver Stegle, Benjamin D Simons, Wolf Reik

Epigenetic-scale comparison of human iPSCs generated by retrovirus, Sendai virus or episomal vectors
Koichiro Nishino, Yoshikazu Arai, Ken Takasawa, Masashi Toyoda, Mayu Yamazaki-Inoue, Tohru Sugawara, Hidenori Akutsu, Ken Nishimura, Manami Ohtaka, Mahito Nakanishi, Akihiro Umezawa

Knockdown of butyrylcholinesterase but not inhibition by chlorpyrifos alters early differentiation mechanisms in human neural stem cells
Angela K. Teithof, Jason R. Richardson, Ronald P. Hart

In situ transcriptome characteristics are lost following culture adaptation of adult cardiac stem cells
Taeyong Kim, Oscar H Echeagaray, Bingyan J Wang, Alexandria Casillas, Kathleen M. Broughton, Bong-Hyun Kim, Mark A Sussman

Insights into the mutational burden of human induced pluripotent stem cells using an integrative omics approach
Matteo D’Antonio, Paola Benaglio, David A. Jakubosky, William W. Greenwald, Hiroko Matsui, Margaret K.R. Donovan, He Li, Erin N. Smith, Agnieszka D’Antonio-Chronowska, Kelly A. Frazer

miR17~92 is essential for the survival of hematopoietic stem and progenitor cells by restraining pro-apoptotic BIM
Kerstin Brinkmann, Craig Hyland, Carolyn A de Graaf, Andreas Strasser, Warren S Alexander, Marco J Herold

Interrupted reprogramming into induced pluripotent stem cells does not rejuvenate human mesenchymal stromal cells
Carolin Goebel, Roman Goetzke, Thomas Eggermann, Wolfgang Wagner

Muscle Stem Cell Niche Dysregulation in Volumetric Muscle Loss Injury
Shannon Anderson, Woojin M Han, Vunya Srinivasa, Mahir Mohiuddin, Marissa A Ruehle, Austin Moon, Eunjung Shin, Cheryl L San Emeterio, Molly E Ogle, Edward A Botchwey, Nick J Willett, Young C Jang

Effective repair of joint cartilage using human pluripotent stem cell-derived tissue
Oliver F.W. Gardner, Subhash Juneja, Heather Whetstone, Yulia Nartiss, Jakob T Sieker, Christian Veillette, Gordon M Keller, April M Craft

Functional Role of Annexins in Zebrafish Caudal Fin Regeneration: A Gene Knockdown Approach in Regenerating Tissue.
Mir Quoseena, Sowmya Vuppaladadium, Shahid Hussain, Swarna Bharathi, Mohammed M Idris

Regulatory T-cells are required for neonatal heart regeneration
Jiatao Li, Kevin Y Yang, Rachel Chun Yee Tam, Vicken W Chan, Bao Sheng, Shohei Hori, Bin Zhou, Yuk Ming Dennis Lo, Kathy O Lui

RAB-5 regulates regenerative axonal fusion by controlling EFF-1 endocytosis
Casey Linton, Brent Neumann, Rosina Giordano-Santini, Massimo A Hilliard

Aberrant Information Transfer Interferes with Functional Axon Regeneration
Chen Ding, Marc Hammarlund

Combined inhibition of apoptosis and necrosis promotes transient neuroprotection of retinal ganglion cells and partial axon regeneration after optic nerve damage
Maki Kayama, Kumiko Omura, Yusuke Murakami, Edith Reshef, Aristomenis Thanos, Yuki Morizane, Andrea Gianni, Toru Nakazawa, Joan Miller, Larry Benowitz, Demetrios Vavvas

Cerebrovascular damages induce lymphatic invasion into brain parenchyma to guide vascular regeneration
Jingying Chen, Jianbo He, Qifen Yang, Yaoguang Zhang, Tianyu Zhao, Deqin Yang, Lingfei Luo

The Drosophila SWI/SNF chromatin-remodeling complexes play separate roles in regulating growth and cell fate during regeneration
Yuan Tian, Rachel K Smith-Bolton

Functional testing of a human PBX3 variant in zebrafish reveals a potential modifier role in congenital heart defects
Gist H. Farr III, Kimia Imani, Darren Pouv, Lisa Maves

Shared gene co-expression networks in autism from induced pluripotent stem cell (iPSC) neurons
Dwaipayan Adhya, Vivek Swarup, Paulina Nowosaid, Carole Shum, Kamila Jozwik, Grainne McAlonan, Maria Andreina Mendez, Jamie Horder, Declan Murphy, Daniel H. Geschwind, Jack Price, Jason Carroll, Deepak P. Srivastava, Simon Baron-Cohen

Complete Disruption of Autism-Susceptibility Genes by Gene-Editing Predominantly Reduces Functional Connectivity of Isogenic Human Neurons
Eric Deneault, Sean H White, Deivid C Rodrigues, Joel Ross, Muhammad Faheem, Kirill Zaslavsky, Zhuozhi Wang, Roumiana Alexandrova, Giovanna Pellecchia, Wei Wei, Alina Piekna, Gaganjot Kaur, Jennifer L Howe, Vickie Kwan, Bhooma Thiruvahindrapuram, Susan Walker, Peter Pasceri, Daniele Merico, Ryan KC Yuen, Karun K Singh, James Ellis, Stephen W Scherer

Cooption of antagonistic RNA-binding proteins establishes cell hierarchy in Drosophila neuro-developmental tumors
Sara Genovese, Raphael Clement, Cassandra Gaultier, Florence Besse, Karine Narbonne-Reveau, Fabrice Daian, Sophie Foppolo, Nuno Miguel Luis, Cédric Maurange

Vascular defects of DYRK1A knockouts are ameliorated by modulating calcium signaling in zebrafish
Jeong-Soo Lee, Hyun-Ju Cho, Jae-Geun Lee, Jong-Hwan Kim, Seon-Young Kim, Yang Hoon Huh, Hyo-Jeong Kim, Kyu-Sun Lee, Kweon Yu

Developmental-stage-specific proliferation and retinoblastoma genesis in RB-deficient human but not mouse cone precursors
Hardeep P Singh, Sijia Wang, Kevin Stachelek, Sunhye Lee, Mark W Reid, Matthew E Thornton, Cheryl Mae Craft, Brendan H Grubbs, David Cobrinik

The pyriproxyfen metabolite 4’OH- pyriproxyfen disrupts thyroid hormone signaling and enhances Musashi-1 levels in neuroprogenitors.
Petra Spirhanzlova, Sebastien Le Mevel, Karn Wejaphikul, Bilal Mughal, Jean-David Gothie, Anthony Sebillot, Lucille Butruille, Michelle Leemans, Theo Visser, Sylvie Remaud, Jean-Baptiste Fini, Barbara Demeneix

Defining Hepatic Modifiers Of ATTR Amyloidosis Through Therapeutic Gene Editing In Patient iPSCs
Richard M Giadone, Derek C Liberti, Taylor M Matte, Nicholas Skvir, Kai-Chun Chen, Jyh-Chang Jean, Andrew A Wilson, Darrell N Kotton, R Luke Wiseman, George J Murphy

Evo-devo & evo

The Ly6/uPAR protein Bouncer is necessary and sufficient for species-specific fertilization
Sarah Herberg, Krista R Gert, Alexander Schleiffer, Andrea Pauli

The genomic basis of colour pattern polymorphism in the harlequin ladybird
Mathieu Gautier, Junichi Yamaguchi, Julien Foucaud, Anne Loiseau, Aurelien Ausset, Benoit Facon, Bernhard Gschloessl, Jacques Lagnel, Etienne Loire, Hugues Parrinello, Danny Severac, Celine Lopez-Roques, Cecile Donnadieu, Maxime Manno, Helene Berges, Karim Gharbi, Lori Lawson-Handley, Lian-Sheng Zang, Heiko Vogel, Arnaud Estoup, Benjamin Prud’homme

Repeated inversions at the pannier intron drive diversification of intraspecific colour patterns of ladybird beetles
Toshiya Ando, Takeshi Matsuda, Kumiko Goto, Kimiko Hara, Akinori Ito, Junya Hirata, Joichiro Yatomi, Rei Kajitani, Miki Okuno, Katsushi Yamaguchi, Masaaki Kobayashi, Tomoyuki Takano, Yohei Minakuchi, Masahide Seki, Yutaka Suzuki, Kentaro Yano, Takehiko Itoh, Shuji Shigenobu, Atsushi Toyoda, Teruyuki Niimi

A revised understanding of Tribolium morphogenesis further reconciles short and long germ development
Matthew Alan Benton

Evolution and developmental diversity of skin spines in pufferfish
Takanori Shono, Alexandre P Thiery, Daisuke Kurokawa, Ralf Britz, Gareth J Fraser

The radial expression of dorsal-ventral patterning genes in placozoans, Trichoplax adhaerens, argues for an oral-aboral axis
Timothy DuBuc, Yuriy Bobkov, Joseph F Ryan, Mark Martindale

CRISPR/Cas9-mediated gene knockin in the hydroid Hydractinia symbiolongicarpus
Steven M Sanders, Zhiwei Ma, Julia M Hughes, Brooke M Riscoe, Gregory A Gibson, Alan M Watson, Hakima Flici, Uri Frank, Christine E Schnitzler, Andreas D Baxevanis, Matthew L Nicotra

A robust method for transfection in choanoflagellates illuminates their cell biology and the ancestry of animal septins
David Booth, Heather Middleton, Nicole King

Transcriptomic atlas of mushroom development highlights an independent origin of complex multicellularity
Krisztina Krizsan, Eva Almasi, Zsolt Merenyi, Neha Sahu, Mate Viragh, Tamas Koszo, Stephen Mondo, Brigitta Kiss, Balazs Balint, Ursula Kues, Kerrie Barry, Judit Cseklye, Botond Hegedus, Bernard Henrissat, Jenifer Johnson, Anna Lipzen, Robin A. Ohm, Istvan Nagy, Jasmyn Pangilinan, Juying Yan, Yi Xiong, Igor V. Grigoriev, David S. Hibbett, Laszlo G. Nagy

Evolutionary trade-offs between unicellularity and multicellularity in budding yeast
Jennie Kuzdzal-Fick, Lin Chen, Gabor Balazsi

De novo origin of multicellularity in response to predation
Matthew D. Herron, Josh M. Borin, Jacob C. Boswell, Jillian Walker, I-Chen Kimberly Chen, Charles A. Knox, Margrethe Boyd, Frank Rosenzweig, William C. Ratcliff

Morphological, cellular and molecular characterization of posterior regeneration in the marine annelid Platynereis dumerilii
Anabelle Planques, Julien Malem, Julio Parapar, Michel Vervoort, eEve Gazave

Miniscule differences between the sex chromosomes in the giant genome of a salamander, Ambystoma mexicanum
Melissa Carol Keinath, Nataliya Timoshevskaya, Vladimir A Timoshevskiy, S. Randal Voss, Jeramiah J Smith

Evolution of salivary glue genes in Drosophila species
Jean-Luc Da Lage, Gregg W. C. Thomas, Magalie Bonneau, Virginie Courtier-Orgogozo

Diet-based assortative mating through sexual imprinting
Emily K. Delaney, Hopi E. Hoekstra

Chromosomal rearrangements as a source of new gene formation in Drosophila yakuba
Nicholas B. Stewart, Rebekah L. Rogers

Medaka population genome structure and demographic history described via genotyping-by-sequencing
Takafumi Katsumura, Shoji Oda, Hiroshi Mitani, Hiroki Oota

Architectural traits constrain the evolution of unisexual flowers and sexual segregation within inflorescences: an interspecific approach
Ruben Torices, Ana Afonso, Arne A. Anderberg, Jose M. Gomez, Marcos Mendez

Integration of anatomy ontologies and evo-devo using structured Markov models suggests a new framework for modeling discrete phenotypic traits
Sergei Tarasov

Cell biology

Separation and Loss of Centrioles from Primordidal Germ Cells to Mature Oocytes in the Mouse
Gerald Schatten, Calvin R Simerly, Marion Manil-Ségalen, Carlos Castro, Carrie Hartnett, Dong Kong, Marie-Helene Verlhac, Jadranka Loncarek

Nuclear actin is required for transcription during Drosophila oogenesis
Maria Sokolova, Henna M Moore, Bina Prajapati, Joseph Dopie, Leena Merilainen, Mikko Honkanen, Rita Cerejeira Matos, Minna Poukkula, Ville Hietakangas, Maria Vartiainen

CDK phosphorylation of Xenopus laevis M18BP1 promotes its metaphase centromere localization
Bradley T French, Aaron F Straight

14-3-3 recruits keratin intermediate filaments to mechanically sensitive cell-cell contacts
Richard A. Mariani, Shalaka Paranjpe, Radek Dobrowolski, Gregory F. Weber

Gene editing can generate fragile bivalents in mouse oocytes
Marion Manil-Ségalen, Małgorzata Łuksza, Joanne Kannaan, Véronique Marthiens, Simon I.R. Lane, Keith T Jones, Marie-Émilie Terret, Renata Basto, Marie-Hélène Verlhac

Microtubule plus-tips act as signaling hubs for positioning the cleavage furrow during cytokinesis.
Vikash Verma, Thomas J Maresca

Systematic Characterization of RhoGEF/RhoGAP Regulatory Proteins Reveals Organization Principles of Rho GTPase Signaling
Paul Markus Mueller, Juliane Rademacher, Richard D Bagshaw, Keziban Merve Alp, Girolamo Giudice, Loise E Heinrich, Carolin Barth, Rebecca L Eccles, Marta Sanchez-Castro, Lennart Brandenburg, Geraldine Mbamalu, Monika Tucholska, Lisa Spatt, Celina Wortmann, Maciej T Czajkowski, Robert William Welke, Sunqu Zhang, Vivian Nguyen, Trendelina Rrustemi, Philipp Trnka, Kiara Freitag, Brett Larsen, Oliver Popp, Philipp Mertins, Chris Bakal, Anne-Claude Gingras, Olivier Pertz, Frederick P Roth, Karen Colwill, Tony Pawson, Evangelia Petsalaki, Oliver Rocks

Stick-slip dynamics of cell adhesion triggers spontaneous symmetry breaking and directional migration
Katharina Hennig, Irene Wang, Philippe Moreau, Leo Valon, Simon De Beco, Mathieu Coppey, Yekaterina Miroshnikova, Corinne Albiges Rizo, Cyril Favard, Raphael Voituriez, martial Balland

Excitable dynamics of Ras triggers self-organized PIP3 signaling for spontaneous cell migration
Seiya Fukushima, Satomi Matsuoka, Masahiro Ueda

Vimentin filaments interact with the mitotic cortex allowing normal cell division
Sofia Duarte, Álvaro Viedma-Poyatos, Elena Navarro-Carrasco, Alma E Martínez, María A Pajares, Dolores Pérez-Sala

Force dependence of filopodia adhesion: involvement of myosin II and formins
Naila O. Alieva, Artem K. Efremov, Shiqiong Hu, Dongmyung Oh, Zhongwen Chen, Meenubharathi Natarajan, Hui Ting Ong, Antoine Jegou, Guillaume Romet-Lemonne, Jay T. Groves, Michael P. Sheetz, Jie Yan, Alexander D. Bershadsky

A combinatorial extracellular code tunes the intracellular signaling network activity to distinct cellular responses
Dmitry Kuchenov, Frederik Ziebell, Florian Salopiata, Mevlut Citir, Ursula Klingmueller, Wolfgang Huber, Carsten Schultz

Modelling

Turing patterns are common but not robust
Natalie S. Scholes, David Schnoerr, Mark Isalan, Michael P. H. Stumpf

Turing-like patterns can arise from purely bioelectric mechanisms
Micah Brodsky

Isolating and Quantifying the Role of Developmental Noise in Generating Phenotypic Variation
Maria A Kiskowski, Tilmann Glimm, Nickolas Moreno, Tony Gamble, Ylenia Chiari

Linear stability analysis of morphodynamics during tissue regeneration in plants
Anne-Mieke Reijne, Gunnar Pruessner, Giovanni Sena

Simulation of morphogen and tissue dynamics
M. D. Peters, L. D. Wittwer, A. Stopka, D. Barac, C. Lang, D. Iber

Stochastic and deterministic modelling of cell migration
Enrico Gavagnin, Christian A. Yates

A simplified multiphase multiscale model for tissue growth
E.C. Holden, B.S. Brook, S.J. Chapman, R.D. O’Dea

Rosette-driven rigidity transition in epithelial tissues
Le Yan, Dapeng Bi

Buckling without bending: a new paradigm in morphogenesis
T. A. Engstrom, Teng Zhang, A. K. Lawton, A. L. Joyner, J. M. Schwarz

Diffusion vs. direct transport in the precision of morphogen readout
Sean Fancher, Andrew Mugler

Gradient Sensing via Cell Communication
Dallas Foster, Collin Victor, Brian Frost, Juan M. Restrepo

Modeling large fluctuations of thousands of clones during hematopoiesis: the role of stem cell self-renewal and bursty progenitor dynamics in rhesus macaque
Song Xu, Sanggu Kim, Irvin S. Y. Chen, Tom Chou

A minimal “push-pull” bistability model explains oscillations between quiescent and proliferative cell states.
Sandeep Krishna, Sunil Laxman

A Statistical Model of Cell Wall Dynamics during Expansive Growth
Shankar Lalitha Sridhar, Joseph K.E. Ortega, Franck Vernerey

Tools & resources

| Imaging etc.

BigStitcher: Reconstructing high-resolution image datasets of cleared and expanded samples
David Hörl, Fabio Rojas Rusak, Friedrich Preusser, Paul Tillberg, Nadine Randel, Raghav K. Chhetri, Albert Cardona, Philipp J. Keller, Hartmann Harz, Heinrich Leonhardt, Mathias Treier, Stephan Preibisch

Predicting local tissue mechanics using immunohistochemistry
David E Koser, Emad Moeendarbary, Stefanie Kuerten, Kristian Franze

Broad applicability of a streamlined Ethyl Cinnamate-based clearing procedure
Wouter Masselink, Daniel Reumann, Prayag Murawala, Pawel Pasierbek, Yuka Taniguchi, Juergen A Knoblich, Elly M Tanaka

Single-embryo and single-blastomere immunoblotting reports protein expression heterogeneity in early-stage preimplantation embryos
Elisabet Rosas, Andrew J Modzelewski, Lin He, Amy E Herr

Fbxo2VHC mouse and embryonic stem cell reporter lines delineate in vitro-generated inner ear sensory epithelia cells and enable otic lineage selection and Cre-recombination
Byron H Hartman, Robert Böscke, Daniel C. Ellwanger, Sawa Keymeulen, Mirko Scheibinger, Stefan Heller

Collagen assembly and turnover imaged with a CRISPR-Cas9 engineered Dendra2 tag
Adam Pickard, Antony Adamson, Yinhui Lu, Joan Chang, Richa Garva, Nigel Hodson, Karl Kadler

Isolating mitotic and meiotic germ cells from male mice by developmental synchronization, staging, and sorting
Katherine A Romer, Dirk G de Rooij, David C Page

Generation of a versatile BiFC ORFeome library for analyzing protein-protein interactions in live Drosophila
Samir Merabet, Johannes Bischof, Marilyne Duffraisse, Edy Furger, Leiore Ajuria, Guillaume Giraud, Solene Vanderperre, Rachel Paul, Mikael Björklund, Damien Ahr, Alexis Ahmed, Lionel Spinelli, Christine Brun, Konrad Basler

DARPins recognizing mTFP1 as novel reagents for in vitro and in vivo protein manipulations
M. Alessandra Vigano, Dimitri Bieli, Jonas V Schaefer, Roman P Jakob, Shinya Matsuda, Timm Maier, Andreas Plueckthun, Markus Affolter

CDeep3M – Plug-and-Play cloud based deep learning for image segmentation of light, electron and X-ray microscopy
Matthias Haberl, Christopher Churas, Lucas Tindall, Daniela Boassa, Sebastien Phan, Eric A Bushong, Matthew Madany, Raffi Akay, Thomas J Deerinck, Steven T Peltier, Mark H Ellisman

Rapid micro fluorescence in situ hybridization in tissue sections
Deborah Huber, Govind V. Kaigala

Evaluation of Deep Learning Strategies for Nucleus Segmentation in Fluorescence Images
Juan C. Caicedo, Jonathan Roth, Allen Goodman, Tim Becker, Kyle W Karhohs, Claire McQuin, Shantanu Singh, Fabian Theis, Anne E. Carpenter

An Organometallic Ir(III) Molecular Probe for Imaging Microtubules in Fluorescence and Electron Microscopy
Xiaohe Tian Battaglia, Cesare De Pace, Lorena Ruiz-Perez, Bo Chen, Rina Su, Mingzhu Zhang, Ruilong Zhang, Qiong Zhang, Qin Wang, Hongping Zhou, Jieying Wu, Giuseppe Battaglia, Zhongping Zhang, Yupeng Tian

Kilohertz frame-rate two-photon tomography
Abbas Kazemipour, Ondrej Novak, Daniel Flickinger, Jonathan S Marvin, Jonathan King, Philip Borden, Shaul Druckmann, Karel Svoboda, Loren L Looger, Kaspar Podgorski

Embryo timelapses can be compiled and quantified to understand canonical histone dynamics across multiple cell cycles.
Lydia Smith, Paul S. Maddox

Convolutional Neural Network-Based Instance Segmentation Algorithm to Acquire Quantitative Criteria of Early Mouse Development
Yuta Tokuoka, Takahiro G Yamada, Noriko Hiroi, Tetsuya J Kobayashi, Kazuo Yamagata, Akira Funahashi

FluoEM: Virtual labeling of axons in 3-dimensional electron microscopy data for long-range connectomics
Florian Drawitsch, Ali Karimi, Kevin M Boergens, Moritz Helmstaedter

DataPackageR: Reproducible data preprocessing, standardization and sharing using R/Bioconductor for collaborative data analysis.
Greg Finak, Bryan Mayer, William Fulp, Paul Obrecht, Alicia Sato, Eva Chung, Drienna Holman, Raphael Gottardo

Forget Pixels: Adaptive Particle Representation of Fluorescence Microscopy Images
Bevan L. Cheeseman, Ulrik Günther, Mateusz Susik, Krzysztof Gonciarz, Ivo F. Sbalzarini

| Genome tools

Efficient single-copy HDR by 5′ modified long dsDNA donors
Jose Arturo Gutierrez-Triana, Thomas Thumberger, Tinatini Tavhelidse, Isabelle Thomas, Beate Wittbrodt, Tanja Kellner, Erika Tsingos, Joachim Wittbrodt

Switchable genome editing via genetic code expansion
Toru Suzuki, Maki Asami, Sanjay G. Patel, Louis Y. P. Luk, Yu-Hsuan Tsai, Anthony C. F. Perry

Spatiotemporally controlled genetic perturbation for efficient large-scale studies of cell non-autonomous effects
Rita Sousa-Nunes, Andrea Chai, Ana M Mateus, Fazal Oozeer

A Drosophila CRISPR/Cas9 toolkit for conditionally manipulating gene expression in the prothoracic gland as a test case for polytene tissues
Kirst King-Jones, Nhan Huynh

An expanded toolkit for gene tagging based on MiMIC and scarless CRISPR tagging in Drosophila
David Li-Kroeger, Oguz Kanca, Pei-Tseng Lee, Sierra Cowan, Michael Lee, Manish Jaiswal, Jose Louis Salazar, Yuchun He, Hugo Bellen

Robust genome editing with short single-stranded and long, partially single-stranded DNA donors in C. elegans
Craig Mello, Gregoriy A Dokshin, Krishna S Ghanta, Katherine M Piscopo

An in vivo translation-reporter system for the study of protein synthesis in zebrafish embryos
Ines Palha, Isabelle Anselme, Sylvie Schneider-Maunoury, Francois Giudicelli

Enhancement of Transgene Expression by NF-Y and CTCF
Devon Zimmerman, Krupa Patel, Matthew Hall, Jacob Elmer

Precise tuning of gene expression output levels in mammalian cells
Yale S. Michaels, Mike B Barnkob, Hector Barbosa, Toni A Baeumler, Mary K Thompson, Violaine Andre, Huw Colin-York, Marco Fritzsche, Uzi Gileadi, Hilary M Sheppard, David JHF Knapp, Thomas A Milne, Vincenzo Cerundolo, Tudor A Fulga

Dynamics and spatial genomics of the nascent transcriptome in single mESCs by intron seqFISH
Sheel Shah, Yodai Takei, Wen Zhou, Eric Lubeck, Jina Yun, Noushin Koulena, Eric J. Liaw, Mina Amin, Long Cai

Branching developmental pathways through high dimensional single cell analysis in trajectory space
Denis Dermadi, Michael Bscheider, Kristina Bjegovic, Nicole H Lazarus, Agata Szade, Husein Hadeiba, Eugene C Butcher

SmartCodes : functionalized barcodes that enable targeted retrieval of clonal lineages from a heterogeneous population
Clare Rebbeck, Florian Raths, Bassem Ben Cheikh, Kenneth Gouin, Gregory Hannon, Simon Knott

Mass-spectrometry of single mammalian cells quantifies proteome heterogeneity during cell differentiation
Bogdan Budnik, Ezra Levy, Guillaume Harmange, Nikolai Slavov

CRISPR-SURF: Discovering regulatory elements by deconvolution of CRISPR tiling screen data
Jonathan Y Hsu, Charles P Fulco, Mitchel A Cole, Matthew C Canver, Danilo Pellin, Falak Sher, Rick Farouni, Kendell Clement, James A Guo, Luca Biasco, Stuart H Orkin, Jesse M Engreitz, Eric S Lander, J. Keith Joung, Daniel E Bauer, Luca Pinello

Scarless gene tagging of transcriptionally silent genes in hiPSCs to visualize cardiomyocyte sarcomeres in live cells
Brock Roberts, Joy Arakaki, Kaytlyn A Gerbin, Haseeb Malik, Angelique Nelson, Melissa C Hendershott, Caroline Hookway, Susan A Ludmann, Irina A Mueller, Ruian Yang, Susanne M Rafelski, Ruwanthi N Gunawardane

A novel PCR method directly quantifies sequence features that block primer extension
Richard M Cawthon

SCuPhr: A Probabilistic Framework for Cell Lineage Tree Reconstruction
Hazal Koptagel, Seong-Hwan Jun, Jens Lagergren

Research practice & education

Researchers preferentially collaborate with same-gendered colleagues across the life sciences
Luke Holman, Claire Morandin

Career Choice, Gender, and Mentor Impact: Results of the U.S. National Postdoc Survey
Sean C. McConnell, Erica L. Westerman, Joseph F. Pierre, Erin J Heckler, Nancy B. Schwartz

Arbitration is needed to resolve scientific authorship disputes

Zen Faulkes

Becoming more transparent: Collecting and presenting data on biomedical Ph.D. alumni

Christopher L Pickett​, Shirley Tilghman

Analysis and Correction of Inappropriate Image Duplication: The Molecular and Cellular Biology Experience
Arturo Casadevall, Elisabeth M Bik, Ferric C Fang, Amy Kullas, Roger J Davis

Reproducible big data science: A case study in continuous FAIRness
Ravi K Madduri, Kyle Chard, Mike D’Arcy, Segun C Jung, Alexis Rodriguez, Dinanath Sulakhe, Eric W Deutsch, Cory Funk, Ben Heavner, Matthew Richards, Paul Shannon, Gustavo Glusman, Nathan Price, Carl Kesselman, Ian Foster

Why not…

A skin pigment compound that also functions as sunglasses for birds
Malgorzata Zawadzka, Beatrix Racz, Dario Ambrosini, Carl Henrik Gorbitz, Jens Preben Morth, Elsa Lundanes, Frode Rise, Amund Ringvold, Steven Ray Wilson

Tool use by four species of Indo-Pacific sea urchins
Glyn Barrett, Dominic Revell, Lucy Harding, Ian Mills, Axelle Jorcin, Klaus M. Stiefel

No support for the sexy-sperm hypothesis in the seed beetle: sons of monandrous females fare better in post-copulatory competition
Kristin A. Hook

(2 votes)

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Applications are invited for a four-year funded PhD studentship to conduct research in developmental neurobiology under the supervision of Dr Alexander Fletcher and Prof. Marysia Placzek at the University of Sheffield.

This project is on the development of the hypothalamus, a brain structure with very similar anatomy across vertebrate species. We know that the hypothalamus is very important for mediating physiological homeostasis, yet its development remains poorly understood. This project will address this through a combination of gain-and loss-of function studies in vivo and ex vivo 3D culture with computational modelling.

This project is a great opportunity for a student interested in developmental neurobiology, who is keen to tackle new techniques and work in a truly interdisciplinary environment, acquiring programming and modelling skills and gaining expertise in tissue culture and imaging.

A four-year fully-funded EPSRC studentship is available to home students (British or EU nationality based in the UK) starting in October 2018. Please get in touch with Alexander Fletcher (a.g.fletcher@sheffield.ac.uk) for more details.

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Unit on Genome Structure and Regulation

We are at the National Institute of Child Health and Human Development (NICHD) at NIH. Our lab is interested in understanding cell lineage differentiation, gene regulation and how non-coding DNA elements and the 3D architecture of chromosomes contribute to these processes during early mouse development.

Learn more at pedrorochalab.org

What we offer:

• Fully-funded postdoc positions for multiple years including health benefits
• Opportunity to start your own research program or lead ongoing projects
• The NIH research community is unparalleled in its size, diversity and resources
• Possibility of living in a diverse, liberal and vibrant city: Washington DC
• Or living in a calm residential area with great schools and good affordable housing , Bethesda and Rockville

Who you are:

• You share our enthusiasm for epigenetics, gene regulation, nuclear organization and mouse development.
• You have PhD-experience in one or more of the following: mouse development, mouse genetics, epigenetics, massively-parallel sequencing techniques or computational biology.

Apply: Send the following to gsrunit@gmail.com:

• 2 paragraph cover letter explaining your scientific trajectory and why you would like to join us.
• CV and email contacts for 3 references.

The NIH is dedicated to building a diverse community in its training and employment programs.

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An engineer position in cell biology and biomaterials is available starting from September 2018 in the group of André Le Bivic, at the Institute of Biology of Development of Marseille (IBDM), France. The project aims at understanding the impact of extracellular matrix stiffness on the development of human colon organoids, and in particular on the crosstalk between the matrix and the polarity complexes. The initial contract will be made for 12 months, with possible extension to up to 2 years.

We are seeking for a highly motivated candidate who will use a wide range of methods to support this interdisciplinary research project on the impact of extracellular matrix stiffness on epithelial morphogenesis. The main tasks of the engineer will be the preparation of organoid cultures in 3D from human colon samples and the development / optimization of different types of biocompatible matrices (collagen, BME, PEG or PAA etc.). Specifically, the job requires expert knowledge in the synthesis of biocompatible polymers. Some knowledge in cell biology (cell culture, transfection and immunostaining) and imaging (confocal microscopy, image analysis) would be a plus. The working language in the laboratory is English. Candidates are expected to be able to communicate in English.

A cover letter, a CV and the names of two referents must be sent to the following addresses: Elsa Bazellières: elsa.bazellieres@univ-amu.fr and André Le Bivic: andre.le-bivic@univ-amu.fr

• Team Webpage

• Announcement in pdf

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The story behind melanocyte BACE2, posted by Yan Zhang and Richard White. You can read our recently published full article at Developmental Cell using this link.

Our story began six years ago when my mentor, Dr. Richard White, opened the zebrafish facility and showed me those swimming creatures. He pointed to one type with pigmented stripes and told me those are wild-type fish named AB. He caught one fish with a net and that fish very quickly jumped out of the net and escaped to a water reservoir, before I could have a closer look at her. I did not know that after that day, I would officially join a fish lab and have days and nights to observe those free swimming, free jumping animals.

That escaped fish has a stunning array of pigment patterns which is composed of three types of pigment cells: black melanophores, yellow or orange xanthophores and silvery iridophores (Parichy, 2003). While the tank next to it is filled with a transparent version, casper, where the black melanophores and the silvery iridophores are absent (White et al., 2008), some of the other fish have fuzzy pigmentation with a black tumor on the back. Those are melanomas due to uncontrolled growth of melanophores (Patton et al., 2005). I was fascinated by how diverse a pigment pattern can look like and why animals evolve them.

Animals do this for a reason. Dolphins and marlin have a darker upper surface and a white lower belly. They countershade themselves so that when seen from the top, the dark dorsal matches with deep water darkness and when seen from the bottom, the light colored belly mixes into a sunlit water above. This is one example of camouflage in front of predators. Female guppies prefer male guppies with more orange coloration, possibly because males fed on high-carotenoid diet could better reject interspecific allografts of scales and resist parasite infection, suggesting they have better immune function (Houde, 1997) – a nice example of how guppies use pigment color as a honest signal for health during sexual selection.

Our interests into Bace2 started when Dr. Richard White found out this gene is highly enriched in human melanoma, suggestive of oncogenic effects. We thought knocking it out would make melanomas less aggressive. But when we got zebrafish Bace2 mutants from the Sanger Center, the melanophores looked a lot “more” aggressive, an initially counterintuitive observation. It turned out this pigment mutant has super elongated melanophore cell projections, a structure named the dendrite. In mammals, melanocytes use these long dendrites to transfer melanin to neighboring keratinocytes, a process involved in tanning response to protect keratinocytes from UV-induced damage (Yamaguchi et al., 2007). Unlike mammals, zebrafish melanophores do not transfer melanin across cells, but instead traffic melanin intracellularly to modulate fish appearance (Logan et al., 2006). When melanin is aggregated around the nucleus, the fish looks lighter, and this typically occurs when fish are raised in a daylight environment. When the fish is raised in dark, melanin tends to be dispersed so that melanin covers more area and fish can match their dark-looking color with the environment. Even though zebrafish no longer use dendrites as a channel for melanin delivery, their melanophores can still be very dendritic especially when young melanophores are still actively developing. They likely use these dendrites for patterning and other ways of communicating with their neighbors. Mature melanophores lose those dendrites for unknown reasons, but not for the bace2 mutant, where their melanophores keep dendricity from embryos to adults (Figure 1).

We were intrigued by this out of control problem and sought to study why. We showed that Bace2 works during melanophore maturation, a time frame when melanophores turn on pigment genes and gain melanin. The question was how does it work? Bace2 is a cell-intrinsic sheddase which modulated cell morphology inside the melanophore lineage. We further sought to find out which protein is cleaved by Bace2 to exhibit all those phenotypes. We had no luck in the beginning. Pmel and Gpnmb are the two initial guesses as both of them are involved in melanin production and PMEL can be cut by BACE2 in mice (Rochin et al., 2013; Shimshek et al., 2016). But we soon found out those two substrates could not explain the melanophore dendricity. The research was stuck for a while. When I was even trying to grab everything I could find in our chemical room and threw them into fish to have a try, Dr. White came to me and said, why don’t we try an unbiased chemical screen?

The breakthrough came with a change in methodology. The chemical screen gave us an unexpected but fruitful hit. We found four chemicals able to convert bace2 mutant melanophores into normal looking ones, all of which converge on the same pathway-one that contains insulin, PI3K and mTOR. We realized this is something never studied before, a new PI3K/mTOR regulator that has a melanophore-specific consequence. All of the pieces came together.  It turned out Bace2 itself cleaves the insulin receptor and this cleavage modulates how many functional insulin receptors are left on the cell membrane. In the mutant fish, Bace2 no longer cleaves it and melanophores have hyperactivated insulin/PI3K/mTOR which drives this uncontrolled dendricity. The driving force came from long distance, as we found that a brain-derived insulin peptide (insb) is the stimulating ligand that feeds into insulin receptor in this context.

There are other consequence associated with uncontrolled dendricity: those bace2 mutant melanophores are actively differentiating, actively dividing and wandering around to ectopic locations (Figure 2). We decided to name this bace2 mutant wanderlust as those melanophores like to explore the world, travel to new sites and are free of constraints.

One thing that emerged from this research is the power of unbiased approaches to a problem. We were stuck for a while, but the screen turned out to be the most efficient and rapid way to get to the answer. It’s one of the greatest things about the zebrafish, and has allowed us to connect things – insulin and melanophores – that would have been hard to guess otherwise.

Bibliography

Houde, A. (1997). Sex, Color, and Mate Choice in Guppies. Princeton University Press.

Logan, D. W., Burn, S. F. and Jackson, I. J. (2006). Regulation of pigmentation in zebrafish melanophores. Pigment Cell Res. 19, 206–213.

Parichy, D. M. (2003). Pigment patterns: fish in stripes and spots. Curr. Biol. 13, R947-50.

Patton, E. E., Widlund, H. R., Kutok, J. L., Kopani, K. R., Amatruda, J. F., Murphey, R. D., Berghmans, S., Mayhall, E. A., Traver, D., Fletcher, C. D. M., et al. (2005). BRAF mutations are sufficient to promote nevi formation and cooperate with p53 in the genesis of melanoma. Curr. Biol. 15, 249–254.

Rochin, L., Hurbain, I., Serneels, L., Fort, C., Watt, B., Leblanc, P., Marks, M. S., De Strooper, B., Raposo, G. and van Niel, G. (2013). BACE2 processes PMEL to form the melanosome amyloid matrix in pigment cells. Proc Natl Acad Sci USA 110, 10658–10663.

Shimshek, D. R., Jacobson, L. H., Kolly, C., Zamurovic, N., Balavenkatraman, K. K., Morawiec, L., Kreutzer, R., Schelle, J., Jucker, M., Bertschi, B., et al. (2016). Pharmacological BACE1 and BACE2 inhibition induces hair depigmentation by inhibiting PMEL17 processing in mice. Sci. Rep. 6, 21917.

White, R. M., Sessa, A., Burke, C., Bowman, T., LeBlanc, J., Ceol, C., Bourque, C., Dovey, M., Goessling, W., Burns, C. E., et al. (2008). Transparent adult zebrafish as a tool for in vivo transplantation analysis. Cell Stem Cell 2, 183–189.

Yamaguchi, Y., Brenner, M. and Hearing, V. J. (2007). The regulation of skin pigmentation. J. Biol. Chem. 282, 27557–27561.

(6 votes)

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4WH Neurogenesis: What Where Why When and How?

Neurogenesis is understood as the process by which neural stem cells (NSCs) produce new neurons. In the adult mammalian brain, this process is known to persist in two restricted locations- the dentate gyrus (DG) region of the hippocampus (see figure below) and the lateral walls of the subventricular zone (Ming and Song, 2011). Neurogenesis has been reported to occur at a high pace during embryonic development, decrease rapidly during growth and maturity, and persist in the adult brain at very low levels. New born neurons in the mature brain have been affiliated with important functions including learning, memory and damage repair.

Currently, researchers are focused on dissecting the mechanisms of neurogenesis in the adult brain to understand its unique self-repair strategies, which in turn have the potential to combat a variety of challenging neurodegenerative disorders. But do we know enough? Realistically, this is just the start of a new era in regenerative medicine, and the ‘Adult Neurogenesis 2018’ conference had just taken us a couple steps forward by showcasing cutting-edge research progress in this field.

Adult Neurogenesis 2018 was organised by Gerd Kempermann in collaboration with Abcam in the beautiful city of Dresden. The meeting was held in at the Center for Regenerative Therapies Dresden (CRTD) (see figure below) which currently hosts eighteen core groups in a network of 87 principal investigators from diverse research institutes on the Dresden campus, with expertise in biomedical fields extending from the biology of cells and tissues to biomaterials to nanoengineering. Gerd welcomed us all and initiated the meeting with a refreshing narrative, briefing us about what history has taught us, where we are headed, and the reason behind the field of adult neurogenesis.

That adult neurogenesis occurs throughout life in mammals including humans has been confirmed by multiple studies and regularly published articles following Joseph Altman and Gopal Das’s original discovery over 50 years ago (Altman and Das, 1965). However, from Santiago Ramón y Cajal’s 90 year old harsh decree of adult brain being devoid of any neurogenesis (Cajal, 1991) to Arturo Alverez-Buylla and colleagues’ 2018 description of undetectable levels of neurogenesis in the adult human hippocampus (Sorrells et al., 2018), the field of adult neurogenesis has faced its fair share of obstacles (Kempermann et al., 2018).

There is a growing need not only to unravel the mystery behind adult neurogenesis, but also  to develop technology that can provide universal and undeniable proof of its very nature, including its existence and features. Kempermann used these key facts to redefine the impact, importance and purpose of adult neurogenesis.

The Adult Neurogenesis 2018 meeting brought together some of the most influential and inspiring minds in the field of neurogenesis including, but not limited to, F. Gage, S. Jessberger, B. Berninger, S. Thuret, A. Schinder, L. Barry-Cuif, F. Calegari and M. Brand. It hosted a total of 24 talks and showcased 98 posters (see figure below) which allowed researchers from various parts of the world to share and connect with each other.

The meeting provided excellent networking opportunities allowing interdisciplinary collaboration which will ultimately lead to increase in pace and quality of scientific research. Therefore, the very existence of the meeting itself, paved a path towards finding the answer to when and how are we going to able to understand and uncover the potential of adult neurogenesis. In this report, I have managed to highlight some of my personal favourites, which undoubtedly does not cover the entirety of topics covered in the meeting.

Heterogeneity: Similar but not identical

The beauty of adult neurogenesis lies in its complex diversity. Our brain contains different types and subtypes of neuronal and glial cells all with unique functions. Moreover, depending upon factors including temporal intracellular gradients, time of birth, localisation and differences in synaptic connections, cells expressing identical protein markers in the brain can show significantly varied functions. Fortunately, recent discoveries highlighting the in-depth heterogenic nature of the immature cells involved in adult neurogenesis have begun to elucidate some of the most challenging questions regarding complexity.

Vijay Adusumilli highlighted the heterogeneity within nestin expressing NSCs of the hippocampus at a given time. Nestin is a prominent NSC marker in vivo as well in vitro. Interestingly, nestin positive DG NSCs can themselves be split into groups based on their intracellular reactive oxygen species (ROS) content. His observations emphasised how intricate differences between NSCs can produce functional diversity of neurogenesis in our brain.

Jason Snyder provided us with details on differences and relationships between adult-born and developmentally-born neurons in the hippocampus. Snyder found that changes in adult neurogenesis were inversely proportional to the activity of developmentally-born neurons. He hypothesized that the interplay between adult and developmentally-born neurons plays an important role in the acquisition and turnover of information in the hippocampus.

Alejandro Schinder gave a refreshing introduction to the intricate neuronal connections of granule cells (GCs) in the DG of the hippocampus. His lab had previously demonstrated that immature GCs of DG undergo biased neuronal activation compared to mature neurons (Marín-Burgin et al., 2012), in contrast to other regions of the hippocampus and neocortex. This functional heterogeneity between mature and immature GCs provides insights into their possible role as pattern integrators and differential decoders of information in the DG.

Together, these talks gave us an idea of how heterogeneity within NSCs, and between NSCs and new born neurons, are key factors to consider during future research in translational neuroscience.

Control or to be controlled?

Expanded research in adult neurogenesis has not only helped us provide an unprecedented surveillance of brain development but has also given us a chance to repair brain damage. Since NSCs are known to be the fundamental units of brain regeneration, recent studies have focused on modulating their behaviour and thereby developing possible therapeutic strategies for neurodegenerative disorders. This meeting was able to showcase some of the important and newly discovered modulators of adult neurogenesis.

• How is it controlled?

Autophagy is an intracellular degradation system for cytosolic proteins and organelles, which is critical for cellular homeostasis (Nixon, 2013). Iris Schäffner and her colleagues investigated the FoxO family of transcription factors with respect to regulation of autophagy in adult hippocampal neurogenesis. Schäffner hypothesized a novel pathway connecting FoxO-dependent autophagic flux to development of adult hippocampal neurons.

Tara Walker talked about how the number of new born DG neurons are kept in check. Regulation of DG neurogenesis involves the death of the majority of new born neurons. She hypothesized that a population of early hippocampal precursor cells die due to ferroptosis, an alternative form of cell death, and thus identified an additional mechanism by which adult hippocampal neurogenesis could be controlled.

Sandra Wendler was able to identify distinct roles of mitochondrial fusion dynamics in the lineage of adult NSCs in the hippocampus. Wendler was able to show that although mitochondrial fusion was dispensable for the proliferative steps of NSCs, this process becomes essential for the maturation and survival of neurons later on.

Sebastian Jessberger shared his discoveries on molecular mechanisms underlying neurogenesis with respect to lipid metabolism. He showed that Fasn, a key enzyme in de novo lipogenesis, was highly active in NSCs (see figure below) (Knobloch et al., 2013). His results provided functional coupling between regulation of lipid metabolism and adult NSC proliferation.

Taken together, these talks provided some key examples of how adult neurogenesis is controlled in the brain. A complete picture of the intricate mechanisms underlying neurogenesis are still unknown. However, piece by piece, we have started understanding the secrets of how new born neurons are created and regulated.

• How can we control it?

Georg Kuhn introduced physical exercise and enriched environment as modulators of adult neurogenesis. Kuhn explained how cardiovascular fitness and exercise are particularly important for prevention, delayed-onset or amelioration of CNS diseases including stroke and dementia (Åberg et al., 2009; Naylor et al., 2008). In parallel, Nora Abrous showed that spatial learning remodels not only new dentate neurons but also creates short term new networks within the hippocampus and long term new networks that extend beyond the hippocampus itself.

Moving deeper in a biological perspective, David Petrik showed how cells regulating adult neurogenesis are responsive to mechanical forces at the tissue level. Increased fluid flow along the walls of the lateral ventricle increased the proliferation of NSCs and this ability was dependent on Epithelial Sodium Channel (ENaC) (Petrik et al., 2018). The flow also controlled calcium oscillations in NSCs on the lateral wall, but not at a deeper niche depth, depicting specific spatial control of neurogenesis by fluid flow.

Federico Calegari took it to the cellular level, exploring whether or not  cognitive impairment could be reversed in old age or compensated throughout life by extrinsically exploiting endogenous NSCs. His lab had previously developed a system that allowed temporal control of cdk4–cyclinD1 overexpression to control the number of neurons produced in vivo (Artegiani et al., 2011). This showed, for the first time, that neurogenesis can be controlled in an acute spatio-temporal manner that allowed to elucidate and control adult neurogenesis.

Taken together, these talks provided examples of how control can be imposed upon neurogenesis in the mammalian brain, both extrinsically and intrinsically. Following on, recent studies have started screening for factors that act as master regulators of NSC homeostasis to understand the extent to which we can control neurogenesis.

The truth to be told

The ultimate objective for unfolding the mysteries and unlocking the potential of adult neurogenesis is to provide a better quality of human life. However, due to the restricted localisation and diluted potential of adult neurogenesis in mammals, not to mention to the lack of human subjects, cellular regenerative therapies for the human brain is proceeding at a considerably slow pace. The conference addressed this issue by showcasing novel technological developments and innovative adaptations of pre-existing biomedical tools which can directly increase the speed and quality of discovery with respect to clinical translation.

Studying the properties of neurogenesis can have significant indirect benefits to clinical medicine. Sandrine Thuret talked about how differential neurogenesis can be used as a biomarker to detect the fate of disease pathology in humans. Her lab showed that differential response of NSCs to patient specific serum can be extended to predict conversion of mildly cognitive impaired patients to Alzheimer’s disease (AD) (Maruszak et al., 2017)

Identification of neurogenic regulators in disease models can serve as key players in restoring healthy physiology in patients with neurodegenerative disorders. Claire Rampon talked about how manipulating mitochondrial properties of new neurons can improve altered cellular properties of an AD mouse brain model and may open new avenues for far-reaching therapeutic strategies for cognitive impairment (Richetin et al., 2017).

Different animal models can have significantly varied neurogenic properties compared to humans which can be particularly useful in developing innovative strategies for human brain repair. Michael Brand talked about how zebrafish is not only an easier model for experimentation, but also provides an excellent source to study adult brain regeneration (Grandel et al., 2006; Kroehne et al., 2011). Brand discussed how zebrafish can be used to study thyroid regulation of adult neurogenesis, emphasising that the genetic factors underlying extensive regeneration in adult zebrafish may be a crucial key to unlock adult brain regeneration in  humans.

Direct reprogramming of adult cells to neurons is an emerging technology which holds great promise for cell-based brain repair. Benedikt Berninger’s lab had identified resident pericytes (a non-neural cell type in the mature brain) to have the potential to be directly converted into neurons (see figure below) (Karow et al., 2012). Berninger talked about the nature of intermediate states taken up by reprogrammed pericytes towards neurogenesis. He showed that as they reprogram, cells pass through a neural stem cell-like state, and that this state is of functional importance for the reprogramming success (Karow et al., 2018-in press). This knowledge may provide new ways for further improving direct reprogramming and in turn, help overcome the scarcity of neurogenesis in the adult mammalian brain.

‘Real-time’ or ‘live’ imaging microscopes allow scientists to observe biological functions of cells and tissues in action. Using an intra-vital imaging procedure, Laure Bally-Cuif showed that her lab was able to dynamically image and track a full population of adult NSCs at a single cell resolution within their niche. This provided the power to deduce live aspects of stem cell behaviour over several weeks in vivo (Dray et al., 2015). Jessberger showed how clonal population derived from neurogenic events can be monitored in vivo using 2-photon microscopy (see figure below) (Pilz et al., 2018). He focused on the importance of using technically straightforward measures to study properties of neurogenesis in its native state.

Fred Gage briefed us about our journey through adult neurogenesis, 2-photon microscopical advances and brain organoids. He showed how human brain organoids can be implanted into mice and observed while it integrates into the rodent CNS (see figure below) (Mansour et al., 2018). The motivation was to find a way to vascularize the human organoid to improve the survival and maturation of these 3-Dimensional human brain tissues to better understand human brain development and study human brain disorders.

Taken together, these talks have emphasised how ground-breaking discoveries coupled with the outstanding development in biomedical technologies has allowed remarkable progress in this field, and provided us with a glimpse into the future and promise of adult neurogenesis.

Conclusion

In light of the recent developments in the field of adult neurogenesis, it is an exhilarating era to exist in. The ‘Adult Neurogenesis 2018’ meeting highlighted many inspiring and pioneering discoveries including insights into neurogenic heterogeneity, control of neurogenesis, and recent technological developments. Neurodegenerative disorders are extremely challenging and expensive to treat. The very discovery of neurogenesis to persist adult mammals including humans has filled us with hope. Given the pace of scientific research, the next few decades might just witness a major leap that humanity can take towards clinical neuroscience.

‘’If I were not in this field today, I would have joined after this conference’’-

Gerd Kempermann

References

Åberg, M.A.I., Pedersen, N.L., Torén, K., Svartengren, M., Bäckstrand, B., Johnsson, T., Cooper-Kuhn, C.M., Åberg, N.D., Nilsson, M., and Kuhn, H.G. (2009). Cardiovascular fitness is associated with cognition in young adulthood. Proc. Natl. Acad. Sci. 106, 20906–20911.

Altman, J., and Das, G.D. (1965). Post-natal origin of microneurones in the rat brain. Nature 207, 953–956.

Artegiani, B., Lindemann, D., and Calegari, F. (2011). Overexpression of cdk4 and cyclinD1 triggers greater expansion of neural stem cells in the adult mouse brain. J. Exp. Med. 208, 937–948.

Cajal, S.R. y (1991). Cajal’s Degeneration and Regeneration of the Nervous System (Oxford University Press).

Dray, N., Bedu, S., Vuillemin, N., Alunni, A., Coolen, M., Krecsmarik, M., Supatto, W., Beaurepaire, E., and Bally-Cuif, L. (2015). Large-scale live imaging of adult neural stem cells in their endogenous niche. Development 142, 3592–3600.

Grandel, H., Kaslin, J., Ganz, J., Wenzel, I., and Brand, M. (2006). Neural stem cells and neurogenesis in the adult zebrafish brain: origin, proliferation dynamics, migration and cell fate. Dev. Biol. 295, 263–277.

Karow, M., Sánchez, R., Schichor, C., Masserdotti, G., Ortega, F., Heinrich, C., Gascón, S., Khan, M.A., Lie, D.C., Dellavalle, A., et al. (2012). Reprogramming of Pericyte-Derived Cells of the Adult Human Brain into Induced Neuronal Cells. Cell Stem Cell 11, 471–476.

Karow, M., Camp, J.G., Falk, S., Gerber, T., Pataskar, A., Gac-Santel, M., Kageyama, J., Brazovskaja, A., Garding, A., Fan, W., et al. (2018). Direct pericyte-to-neuron reprogramming via unfolding of a neural stem cell-like program. Nat Neurosci. Jun 18. doi: 10.1038/s41593-018-0168-3. [Epub ahead of print]

Kempermann, G., Gage, F.H., Aigner, L., Song, H., Curtis, M.A., Thuret, S., Kuhn, H.G., Jessberger, S., Frankland, P.W., Cameron, H.A., et al. (2018). Human Adult Neurogenesis: Evidence and Remaining Questions. Cell Stem Cell. April 18. doi: 10.1016/j.stem.2018.04.004. [Epub ahead of print].

Knobloch, M., Braun, S.M.G., Zurkirchen, L., von Schoultz, C., Zamboni, N., Araúzo-Bravo, M.J., Kovacs, W.J., Karalay, O., Suter, U., Machado, R.A.C., et al. (2013). Metabolic control of adult neural stem cell activity by Fasn-dependent lipogenesis. Nature 493, 226–230.

Kroehne, V., Freudenreich, D., Hans, S., Kaslin, J., and Brand, M. (2011). Regeneration of the adult zebrafish brain from neurogenic radial glia-type progenitors. Development 138, 4831–4841.

Mansour, A.A., Gonçalves, J.T., Bloyd, C.W., Li, H., Fernandes, S., Quang, D., Johnston, S., Parylak, S.L., Jin, X., and Gage, F.H. (2018). An in vivo model of functional and vascularized human brain organoids. Nat. Biotechnol. 36, 432–441.

Marín-Burgin, A., Mongiat, L.A., Pardi, M.B., and Schinder, A.F. (2012). Unique Processing During a Period of High Excitation/Inhibition Balance in Adult-Born Neurons. Science 335, 1238–1242.

Maruszak, A., Murphy, T., Liu, B., Lucia, C. de, Douiri, A., Nevado, A.J., Teunissen, C.E., Visser, P.J., Price, J., Lovestone, S., et al. (2017). Cellular phenotyping of hippocampal progenitors exposed to patient serum predicts conversion to Alzheimer’s Disease. BioRxiv 175604.

Ming, G., and Song, H. (2011). Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions. Neuron 70, 687–702.

Naylor, A.S., Bull, C., Nilsson, M.K.L., Zhu, C., Björk-Eriksson, T., Eriksson, P.S., Blomgren, K., and Kuhn, H.G. (2008). Voluntary running rescues adult hippocampal neurogenesis after irradiation of the young mouse brain. Proc. Natl. Acad. Sci. 105, 14632–14637.

Nixon, R.A. (2013). The role of autophagy in neurodegenerative disease. Nat. Med. 19, 983–997.

Petrik, D., Myoga, M.H., Grade, S., Gerkau, N.J., Pusch, M., Rose, C.R., Grothe, B., and Götz, M. (2018). Epithelial Sodium Channel Regulates Adult Neural Stem Cell Proliferation in a Flow-Dependent Manner. Cell Stem Cell 22, 865-878.e8.

Pilz, G.-A., Bottes, S., Betizeau, M., Jörg, D.J., Carta, S., Simons, B.D., Helmchen, F., and Jessberger, S. (2018). Live imaging of neurogenesis in the adult mouse hippocampus. Science 359, 658–662.

Richetin, K., Moulis, M., Millet, A., Arràzola, M.S., Andraini, T., Hua, J., Davezac, N., Roybon, L., Belenguer, P., Miquel, M.-C., et al. (2017). Amplifying mitochondrial function rescues adult neurogenesis in a mouse model of Alzheimer’s disease. Neurobiol. Dis. 102, 113–124.

Sorrells, S.F., Paredes, M.F., Cebrian-Silla, A., Sandoval, K., Qi, D., Kelley, K.W., James, D., Mayer, S., Chang, J., Auguste, K.I., et al. (2018). Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults. Nature 555, 377–381.

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In May we ran a competition to find a meeting reporter for Development’s upcoming meeting on human development and stem cells.

We had some wonderful entries from across the field, and are delighted today to announce the winner: Antonio Barral Gil, a PhD student in Miguel Manzanares’ Lab at CNIC (The Spanish Center for Cardiac Research) in Madrid. Entrants were tasked with writing a short piece on the state of the field, and Antonio’s piece impressed the judges (the Node’s Community Manager Aidan Maartens and Development’s Executive Editor Katherine Brown) for its energy and excitement, as well as its style and content.

Congratulations Antonio!

Antonio obtained his Degree in Biotechnology in 2015 from the Universidad Pablo de Olavide (Sevilla). He then moved to Madrid, where in 2017 he got his Master’s in Molecular Biomedicine at the Universidad Autónoma de Madrid thanks to a CNIC scholarship. He carried out his Master’s thesis in Miguel Manzanares’ lab, focusing on characterizing the role of the transcription factor NANOG during gastrulation. He has recently started his PhD at the same lab, this time focusing on heart regeneration and development. 

The meeting will be held in September; look out for Antonio’s report soon after!

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The López-Schier laboratory at the Helmholtz Zentrum Munich in Germany is seeking creative and highly motivated PhD students or postdoctoral scholars to work within our group of 9 graduate students and postdoctoral fellows. The working language of the laboratory is English.

Our group focuses on understanding the development, regeneration and function of sensory systems. We use the zebrafish as experimental model, and integrate molecular, cellular, behavioural and clinical data. We also have developed new technical approaches to understand organogenesis, including cell-fate acquisition after regeneration from tissue-resident progenitor cells. Mutations in many of the genes that we have identified are responsible for neurological diseases and cancer.

We currently have a fully funded opening for the following projects:

1. Cellular and genetic bases of organogenesis, including cell packing and tissue remodelling. This project combines single-cell transcriptional profiling, genome engineering using CRISPR/Cas9 and quantitative live imaging data by light-sheet microscopy. Preference will be given to candidates with theoretical or practical knowledge in cell biology or biophysics.

2. Control of cell number, organ size and proportions. Using state of the art high-resolution cell tracking, optogenetics, genome engineering and machine learning, we attempt to understand how cells self-organize and to predict cellular behavior during the regenerative response after tissue injury. This project is ideal for a candidate with a background in physics or engineering and a good command of computer programming.

Qualifications & skills

– University studies in biology-related sciences, physics, engineering or computer science (PhD)

– Ideally having recently completed or about to complete a PhD (Postdoctoral)

– Having published or likely to publish at least one first-author paper in a

first/second tier journal (Postdoctoral)

– Candidates for all position should have a strong inner drive, independence, and willingness to work in a highly interdisciplinary team

– A good command of the English language is essential

Laboratory

The team’s projects are interdisciplinary, and are aimed at understanding the basic rules that allow sensory systems to develop, regenerate and function. We use confocal, spinning-disc and light-sheet microscopy imaging, biochemistry, genome engineering by CRISPR/Cas9, laser nanosurgery, optogenetics, and machine learning.

Environment

The Helmholtz Zentrum in an innovative, well-equipped and scientifically stimulating élite research centre located in the outskirts of Munich, one of the most attractive and innovative major cities in Germany. Situated at the foothills of the Alps, Munich is a cosmopolitan city that has ranked among those with the highest quality of life in Europe.

Contact

Please, apply via electronic mail only, including a cover letter with a short statement of research interests and motivation, a Curriculum Vitae including a list of names and email-addresses for two/three academic references, to:

Dr. Hernán López-Schier

Research Unit Sensory Biology & Organogenesis

Helmholtz Zentrum München
Ingolstädter Landstrasse 1
85764 Neuherberg – Munich, Germany

E-mail: hernan.lopez-schier@helmholtz-muenchen.de

Website: http://lopez-schier.strikingly.com

https://www.gsn.uni-muenchen.de/people/faculty/associate/lopez-schier/index.html

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In early June, a group of 30 world-leading experts came together thanks to an invitation by the Company of Biologists to Wiston House (Sussex, UK) to discuss our current understanding about evolutionary and molecular mechanisms that contributed to developing the specific qualities of our human brains.

Fortunately, the Company of Biologists offers fully funded participation for up to ten young career scientists to attend these workshops, and I had the honor to take part in this extraordinary event. The workshop excelled at what many conferences strive for, but only few achieve: open discussion of unpublished data and the big outstanding questions in the field. What I as a youngster appreciated most about the experience was the accepting atmosphere during discussions on- and offline, which was aided by the young participants being offered the same amount of time to present their work in talks as the senior scientists. This even playing field fueled optimism and inspiration for future cross-disciplinary collaborations. This was further facilitated by the workshop bringing together people working on many different aspects of human brain evolution and development: geneticists, to molecular and cellular biologists, behavioralists, anthropologists, mathematicians and engineers.  All were united in the goal of understanding how our brain turned out to be so strikingly different, but also in some aspects so similar, when compared to other mammalian species.

I much appreciated the interspersed discussion sessions led by the three organizers, Arnold Kriegstein, Victor Borrell and Wieland Huttner, which pushed the leading edge of the field to inspire creative thoughts about new directions to take. The participants scratched their heads and engaged in lively discussions concerning some of the big new findings in the field and how to integrate those across scales of investigation from genetics to biophysical models and behavioral outcomes. For instance, we discussed the origin and implications of having a folded cortex with gyri and sulci, their variability and inheritance, whether or not cortical folding is “simply” an epiphenomenon that is only mechanically induced, and what the temporal relationship between folding and connectivity may be. Participants presented interesting data on model systems to approach these questions, including exciting work on brain diseases related to folding and ferrets as a suitable and tractable animal model of a folded brain. Relatedly, when it comes to recent technological advances concerning model systems for human brain development, organoids, three-dimensional cellular networks derived from human ES or induced pluripotent stem cells, are a highly intriguing opportunity that allows for genetic accessibility and experimental control recapitulating many of the early steps of in vivocortical development. It is certainly an exciting time for this technology, which has the potential to fruitfully contribute to our understanding of genetic and cellular events that shape early circuit formation in human neuronal networks.

Throughout the course of the workshop, a lot of emphasis was put on the unique proliferative events that allow for the human brain to accumulate its staggering number of neurons. In the closing discussion session, it was discussed that on top of the sheer number of neurons, it will be important to further our understanding of how different cell types with human-specific molecular signatures contribute to certain traits of the human brain. Relatedly, understanding how synapses and neuronal connectivity may have been shaped differently during human evolution will help our understanding of functional consequences of early developmental events thought to be unique to humans.

Altogether, I am tremendously grateful for having been given the opportunity to attend this workshop and follow the inspiring discussions that certainly broadened my perspective and gave a sense of where the field will move to in the years to come. Wiston House is an amazing place for an event like this, peaceful and remote, in a beautiful landscape that cannot help but inspire creative thinking and groundbreaking new collaborations through thought-sharing. I cannot thank the Company of Biologists, and Wiston House staff enough for providing this unexampled setting to answer unique questions about the mysteries of the past and present existence of our elusive human brains.

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The University of Helsinki is a leading Nordic university with a strong life science research. The Michon research team (http://www.biocenter.helsinki.fi/bi/michon) is located in the Institute of Biotechnology (http://www.biocenter.helsinki.fi/bi/), which is promoting cutting edge research in the biomedical field.
Our team is interested in the epithelial cell behaviour in murine cornea and incisor renewal.

We are currently looking for a postdoctoral researcher

Our future team mate should have
– a PhD in a relevant biomedical discipline with a strong academic track record
– first-author research paper(s) in internationally recognized, peer-reviewed journal(s)
– demonstrated research background in in and ex vivo strategies
– a good experience with mouse handling
– a resourceful attitude and excellent interpersonal skills: capable of contributing to collaborative projects, as well being able to work and plan independently
– critical thinking skills and excellent English communication skills (written, verbal)
– good knowledge of statistics and commitment to rigorous experimental standards

A strong candidate has
– background on epithelial cell biology and developmental biology
– expertise on histology, in situ hybridization, immunostaining
– strong experience with confocal microscopy, image analysis
– a good training on Photoshop and Illustrator

The successful candidate will be proposed an initial 1+1-year contract. However, the candidate will be strongly supported to apply for funding to gain scientific and financial independency. Salary will be commensurate with the credentials and previous experience of the post-doctoral researcher.

The application should be submitted as a single PDF file containing nothing else than
– a cover letter (max 1 page)
– a CV (max 2 pages)
– a statement of previous achievements (max 2 pages)
– a list of publications
– contact information for three referees

Applications should be emailed to frederic.michon@helsinki.fi before the 1st of August. The shortlisted candidates will be interviewed by Skype by mid-August.

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