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

This month features a host of preprints on human development at the single cell level (perhaps all submitted in time for Development’s September meeting?), plus insights into how butterflies make clear wings and how worms achieve meiosis, and a whole lot more. Preprints hosted on bioRxiv and arXiv – use these links to get to the section you want.

Developmental biology

| Patterning & signalling

| Morphogenesis & mechanics

| Genes & genomes

| Stem cells, regeneration & disease modelling

| Plant development

Evo-devo & evo

Cell biology

Modelling

Tools & resources

Research practice & education

Developmental biology

| Patterning & signalling

Fgf/Ets signalling in Xenopus ectoderm initiates neural induction and patterning in an autonomous and paracrine manners
Ikuko Hongo, Harumasa Okamoto

FGF signaling in development beyond canonical pathways
Ayan T. Ray, Pierre Mazot, J. Richard Brewer, Catarina Catela, Colin J. Dinsmore, Philippe Soriano

Notch controls arterialization by regulating the cell cycle and not differentiation
Wen Luo, Irene Garcia-Gonzalez, Macarena Fernandez-Chacon, Veronica Casquero-Garcia, Rui Benedito

Asymmetric neurogenic commitment of retinal progenitors is regulated via the Notch endocytic pathway
Elisa Nerli, Mauricio Rocha-Martins, Caren Norden

Notch-Directed Germ Cell Proliferation Is Mediated by Proteoglycan-Dependent Transcription
Sandeep Gopal, Aqilah Amran, Andre Elton, Leelee Ng, Roger Pocock

Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart
Thomas J. Cahill, Xin Sun, Christophe Ravaud, Cristina Villa del Campo, Konstantinos Klaourakis, Irina-Elena Lupu, Allegra M. Lord, Cathy Browne, Sten Eirik W. Jacobsen, David R. Greaves, David G. Jackson, Sally A. Cowley, William James, Robin P. Choudhury, Joaquim Miguel Vieira, Paul R. Riley

Pericytes Directly Communicate with Emerging Endothelial Cells During Vasculogenesis
Laura Beth Payne, Bhanu Tewari, Logan Dunkenberger, Samantha Bond, Alyssa Savelli, Jordan Darden, Huaning Zhao, Michael Powell, Kenneth Oestreich, Harald Sontheimer, Sophie Dal-Pra, John C. Chappell

Circadian timing-dependent myoblast differentiation and muscle regeneration
Nobuko Katoku-Kikyo, Ellen Paatela, Daniel L. Houtz, Britney Lee, Dane Munson, Xuerui Wang, Mohammed Hussein, Jasmeet Bhatia, Seunghyun Lim, Ce Yuan, Yoko Asakura, Atsushi Asakura, Nobuaki Kikyo

An endogenous scaling mechanism in zebrafish appendages that controls two-pore potassium-leak channel activity to regulate morphogen and growth factor transcription
Chao Yi, Tim WGM Spitters, Ezz Al-Din Ahmed Al-Far, Sen Wang, Simian Cai, Xin Yan, Kaomei Guan, Michael Wagner, Ali El-Armouche, Christopher L. Antos

Variability of an early developmental cell population underlies stochastic laterality defects
Roberto Moreno-Ayala, Pedro Olivares-Chauvet, Ronny Schäfer, Jan Philipp Junker

Characterizing the diverse cells that associate with the developing commissures of the zebrafish forebrain
J. Schnabl, M.P.H. Litz, C. Schneider, N. PenkoffLidbeck, S. Bashiruddin, M.S. Schwartz, K. Alligood, M.J.F. Barresi

Programmed cell senescence in the mouse developing spinal cord and notochord
Jorge Antolio Domínguez-Bautista, Pilar Sarah Acevo-Rodríguez, Susana Castro-Obregón

Incoherent feedforward regulation via Sox9 and Erk underpins mouse tracheal cartilage development
Takuya Yoshida, Michiyuki Matsuda, Tsuyoshi Hirashima

The neocortical progenitor specification program is established through combined modulation of SHH and FGF signaling
Odessa R. Yabut, Hui-Xuan Ng, Keejung Yoon, Jessica C. Arela, Thomas Ngo, Samuel J. Pleasure

Expression of Wnt5a defines the major progenitors of fetal and adult Leydig cells
Herta Ademi, Isabelle Stévant, Chris M Rands, Béatrice Conne, Serge Nef

CAMSAP3 is required for mTORC1-dependent ependymal cell growth and lateral ventricle shaping in mouse brains
Toshiya Kimura, Hiroko Saito, Miwa Kawasaki, Masatoshi Takeichi

BMP signalling directs a fibroblast-to-myoblast conversion at the connective tissue/muscle interface to pattern limb muscles
Joana Esteves de Lima, Cédrine Blavet, Marie-Ange Bonnin, Estelle Hirsinger, Glenda Comai, Laurent Yvernogeau, Léa Bellenger, Sébastien Mella, Sonya Nassari, Catherine Robin, Ronen Schweitzer, Claire Fournier-Thibault, Shahragim Tajbakhsh, Frédéric Relaix, Delphine Duprez

Intraneuronal chloride accumulation via NKCC1 is not essential for hippocampal network development in vivo
Jürgen Graf, Chuanqiang Zhang, Stephan Lawrence Marguet, Tanja Herrmann, Tom Flossmann, Robin Hinsch, Vahid Rahmati, Madlen Guenther, Christiane Frahm, Anja Urbach, Ricardo Melo Neves, Otto W. Witte, Stefan J. Kiebel, Dirk Isbrandt, Christian A. Hübner, Knut Holthoff, Knut Kirmse

Astrocyte-neuron crosstalk through Hedgehog signaling mediates cortical circuit assembly
Yajun Xie, Aaron T. Kuan, Wengang Wang, Zachary T. Herbert, Olivia Mosto, Olubusola Olukoya, Manal Adam, Steve Vu, Minsu Kim, Nicolás Gómez, Diana Tran, Claire Charpentier, Ingie Sorour, Michael Y. Tolstorukov, Bernardo L. Sabatini, Wei-Chung Allen Lee, Corey C. Harwell

Intrauterine growth restriction causes cellular, molecular, and behavioral deficits consistent with abnormal dentate gyrus neurogenesis in mice
Ashley S. Brown, Matthew Wieben, Shelby Murdock, Jill Chang, Maria Dizon, Richard I. Dorsky, Camille M. Fung

Intrinsic neuronal activity during migration controls the recruitment of specific interneuron subtypes in the postnatal mouse olfactory bulb
Bugeon Stéphane, Haubold Clara, Ryzynski Alexandre, Cremer Harold, Platel Jean-Claude

The BMP antagonist Gremlin1 contributes to the development of cortical excitatory neurons, motor balance and fear responses
Mari Ichinose, Nobumi Suzuki, Tongtong Wang, Hiroki Kobayashi, Laura Vrbanac, Jia Q Ng, Josephine A Wright, Tamsin R M Lannagan, Krystyna A Gieniec, Martin Lewis, Ryota Ando, Atsushi Enomoto, Simon Koblar, Paul Thomas, Daniel L Worthley, Susan L Woods

Retracing Schwann cell developmental transitions in embryonic dissociated DRG cultures
Venkat Krishnan Sundaram, Rasha Barakat, Charbel Massaad, Julien Grenier

The presynaptic glycine transporter GlyT2 is regulated by the Hedgehog pathway in vitro and in vivo
A. de la Rocha-Muñoz, E. Núñez, S. Gómez-López, B. López-Corcuera, J. de Juan-Sanz, C. Aragón

Minimal structural elements required for midline repulsive signaling and regulation of Drosophila Robo1
Haley E. Brown, Timothy A. Evans

Differential activation of JAK-STAT signaling in blood cell progenitors reveals functional compartmentalization of the Drosophila lymph gland
Diana Rodrigues, Yoan Renaud, K. VijayRaghavan, Lucas Waltzer, Maneesha S. Inamdar

Dense reconstruction of elongated cell lineages: overcoming suboptimum lineage encoding and sparse cell sampling
Ken Sugino, Rosa L. Miyares, Isabel Espinosa-Medina, Hui-Min Chen, Christopher J Potter, Tzumin Lee

Non-apoptotic caspase activation sustains ovarian somatic stem cell functions by modulating Hedgehog-signalling and autophagy
Alessia Galasso, Daria Iakovleva, Luis Alberto Baena-Lopez

Widespread non-apoptotic activation of Drosophila Caspase-2/9 limits JNK signaling, macrophage proliferation, and growth of wound-like tumors
Derek Cui Xu, Kenneth M. Yamada, Luis Alberto Baena-Lopez

Ecdysone regulates the Drosophila imaginal disc epithelial barrier, determining the duration of regeneration checkpoint delay
Danielle DaCrema, Rajan Bhandari, Faith Karanja, Ryunosuke Yano, Adrian Halme

Twist regulates Yorkie to guide lineage reprogramming of syncytial alary muscles
Marcel Rose, Jakob Bartle-Schultheis, Katrin Domsch, Ingolf Reim, Christoph Schaub

Yorkie-independent negative feedback couples Hippo pathway activation with Kibra degradation
Sherzod A. Tokamov, Ting Su, Anne Ullyot, Richard G. Fehon

Enhancers with cooperative Notch binding sites are more resistant to regulation by the Hairless co-repressor
Yi Kuang, Anna Pyo, Natanel Eafergan, Brittany Cain, Lisa M. Gutzwiller, Ofri Axelrod, Ellen K. Gagliani, Matthew T. Weirauch, Raphael Kopan, Rhett A. Kovall, David Sprinzak, Brian Gebelein

JAK/STAT pathway promotes Drosophila neuroblast proliferation via the direct CycE regulation
Lijuan Du, Jian Wang

Raising the Connectome: the emergence of neuronal activity and behavior in Caenorhabditis elegans
Bradly Alicea

| Morphogenesis & mechanics

Deterministic and stochastic rules of branching govern dendritic morphogenesis of sensory neurons
Amrutha Palavalli, Nicolás Tizón-Escamilla, Jean-François Rupprecht, Thomas Lecuit

Epidermal PAR-6 and PKC-3 are essential for postembryonic development of Caenorhabditis elegans and control non-centrosomal microtubule organization
Victoria G. Castiglioni, Helena R. Pires, Rodrigo Rosas Bertolini, Amalia Riga, Jana Kerver, Mike Boxem

Myofibril and mitochondria morphogenesis are coordinated by a mechanical feedback mechanism in muscle
Jerome Avellaneda, Clement Rodier, Fabrice Daian, Thomas Rival, Nuno Miguel Luis, Frank Schnorrer

Basal epidermis collective migration and local Sonic hedgehog signaling promote skeletal branching morphogenesis in zebrafish fins
Joshua A. Braunstein, Amy E. Robbins, Scott Stewart, Kryn Stankunas

Cytokinetic abscission is part of the mid-blastula transition switch in early zebrafish embryogenesis
Shai Adar-Levor, Dikla Nachmias, Shani T. Gal-Oz, Yarden M. Jahn, Nadine Peyrieras, Assaf Zaritsky, Ramon Y. Birnbaum, Natalie Elia

The formin Fmn2 is required for the development of an excitatory interneuron module in the zebrafish acoustic startle circuit
Dhriti Nagar, Tomin K James, Ratnakar Mishra, Shrobona Guha, Aurnab Ghose

ARHGEF18/p114RhoGEF coordinates PKA/CREB signaling and actomyosin remodeling to drive trophoblast cell-cell fusion during placenta morphogenesis
Robert Beal, Ana Alonso-Carriazo Fernandez, Dimitris K. Grammatopoulos, Karl Matter, Maria S. Balda

DRAXIN regulates interhemispheric fissure remodelling to influence the extent of corpus callosum formation
Laura Morcom, Timothy J Edwards, Eric Rider, Dorothy Jones-Davis, Jonathan WC Lim, Kok-Siong Chen, Ryan Dean, Jens Bunt, Yunan Ye, llan Gobius, Rodrigo Suárez, Simone Mandelstam, Elliott H Sherr, Linda J Richards

Neural tube closure requires the endocytic receptor Lrp2 and its functional interaction with intracellular scaffolds
Izabela Kowalczyk, Chanjae Lee, Elisabeth Schuster, Josefine Hoeren, Valentina Trivigno, Levin Riedel, Jessica Görne, John B. Wallingford, Annette Hammes, Kerstin Feistel

Fibroblast fusion to the muscle fiber regulates myotendinous junction formation
Wesal Yaseen-Badarneh, Ortal Kraft-Sheleg, Shelly Zaffryar-Eilot, Shay Melamed, Chengyi Sun, Douglas P. Millay, Peleg Hasson

Gradual centriole maturation associates with the mitotic surveillance pathway in mouse development
Cally Xiao, Marta Grzonka, Charlotte Gerards, Miriam Mack, Rebecca Figge, Hisham Bazzi

Knockout of the gene encoding the extracellular matrix protein SNED1 results in early neonatal lethality and craniofacial malformations
Anna Barqué, Kyleen Jan, Emanuel De La Fuente, Christina L. Nicholas, Richard O. Hynes, Alexandra Naba

PAK3 controls the tangential to radial migration switch of cortical interneurons by coordinating changes in cell shape and polarity
Lucie Viou, Pierre Launay, Véronique Rousseau, Justine Masson, Clarisse Pace, Robert S. Adelstein, X. Ma, Zhengping Jia, Fujio Murakami, Jean-Vianney Barnier, Christine Métin

Epidermal stratification is uncoupled from centrosome-dependent cell division orientation of the basal progenitors
Mareike Damen, Ekaterina Soroka, Houda Khatif, Christian Kukat, Benjamin D. Simons, Hisham Bazzi

Interplay between medial nuclear stalling and lateral cellular flow underlies cochlear duct spiral morphogenesis
Mamoru Ishii, Tomoko Tateya, Michiyuki Matsuda, Tsuyoshi Hirashima

The effect of absent blood flow on the zebrafish cerebral and trunk vasculature
Elisabeth Kugler, Ryan Snodgrass, George Bowley, Karen Plant, Jovana Serbanovic-Canic, Paul C. Evans, Timothy Chico, Paul Armitage

Axon guidance at the midline – a live imaging perspective
Alexandre Dumoulin, Nikole R. Zuñiga, Esther T. Stoeckli

Drosophila USP22/non-stop regulates the Hippo pathway to polarise the actin cytoskeleton during collective border cell migration
Hammed Badmos, Neville Cobbe, Amy Campbell, Daimark Bennett

Astral microtubule crosslinking by Feo safeguards uniform nuclear distribution in the Drosophila syncytium
Ojas Deshpande, Jorge de-Carvalho, Diana V. Vieira, Ivo A. Telley

3D MAPs discovers the morphological sequence chondrocytes undergo in the growth plate and the regulatory role of GDF5 in this process
Sarah Rubin, Ankit Agrawal, Johannes Stegmaier, Jonathan Svorai, Yoseph Addadi, Paul Villoutreix, Tomer Stern, Elazar Zelzer

EHBP1 and EHD2 regulate Dll4 caveolin-mediated endocytosis during blood vessel development
Amelia M Webb, Caitlin R Francis, Jayson M Webb, Hayle Kincross, Keanna M Lundy, Rachael Judson, Dawn Westhoff, Stryder M Meadows, Erich J Kushner

Epithelial layer unjamming shifts energy metabolism toward glycolysis
Stephen J. DeCamp, Victor M.K. Tsuda, Jacopo Ferruzzi, Stephan A. Koehler, John T. Giblin, Darren Roblyer, Muhammad H. Zaman, Nicolas Chiu Ogassavara, Jennifer Mitchel, James P. Butler, Jeffrey J. Fredberg

Control and mechanisms of pulsatile flows in epithelial monolayers
Raghavan Thiagarajan, Alka Bhat, Guillaume Salbreux, Mandar M. Inamdar, Daniel Riveline

Cell cycle-dependent active stress drives epithelia remodeling
John Devany, Daniel M. Sussman, M. Lisa Manning, Margaret L. Gardel

| Genes & genomes

The First Mitotic Division of the Human Embryo is Highly Error-prone
Emma Ford, Cerys E. Currie, Deborah M. Taylor, Muriel Erent, Adele L. Marston, Geraldine M. Hartshorne, Andrew D. McAinsh

A spatially resolved single cell atlas of human gastrulation
Richard C.V. Tyser, Elmir Mahammadov, Shota Nakanoh, Ludovic Vallier, Antonio Scialdone, Shankar Srinivas

A single cell atlas of human cornea that defines its development, limbal stem and progenitor cells and the interactions with the limbal niche
Joseph Collin, Rachel Queen, Darin Zerti, Sanja Bojic, Nicky Moyse, Marina Moya Molina, Chunbo Yang, Gary Reynolds, Rafiqul Hussain, Jonathan M Coxhead, Steven Lisgo, Deborah Henderson, Agatha Joseph, Paul Rooney, Saurabh Ghosh, Che Connon, Muzlifah Haniffa, Francisco Figueiredo, Lyle Armstrong, Majlinda Lako

Spatial and single-cell transcriptional landscape of human cerebellar development
Kimberly A. Aldinger, Zach Thomson, Parthiv Haldipur, Mei Deng, Andrew E. Timms, Matthew Hirano, Gabriel Santpere, Charles Roco, Alexander B. Rosenberg, Belen Lorente-Galdos, Forrest O. Gulden, Diana O’Day, Lynne M. Overman, Steven N. Lisgo, Paula Alexandre, Nenad Sestan, Dan Doherty, William B. Dobyns, Georg Seelig, Ian A. Glass, Kathleen J. Millen

Single-cell sequencing of human iPSC-derived cerebellar organoids shows recapitulation of cerebellar development
Samuel Nayler, Devika Agarwal, Fabiola Curion, Rory Bowden, Esther B.E. Becker

An organoid and multi-organ developmental cell atlas reveals multilineage fate specification in the human intestine
Qianhui Yu, Umut Kilik, Emily M. Holloway, Yu-Hwai Tsai, Angeline Wu, Joshua H. Wu, Michael Czerwinski, Charlie Childs, Zhisong He, Ian A. Glass, Peter D. R. Higgins, Barbara Treutlein, Jason R. Spence, J. Gray Camp

A semi-automated intestinal organoid screening method demonstrates epigenetic control of epithelial maturation
Jenny Ostrop, Rosalie Zwiggelaar, Marianne Terndrup Pedersen, François Gerbe, Korbinian Bösl, Håvard T. Lindholm, Alberto Díez-Sánchez, Naveen Parmar, Silke Radetzki, Jens Peter von Kries, Philippe Jay, Kim B. Jensen, Cheryl Arrowsmith, Menno J. Oudhoff

Unravelling the developmental roadmap towards human brown adipose tissue
Stefania Carobbio, Anne-Claire Guenantin, Myriam Bahri, Isabella Samuelson, Floris Honig, Sonia Rodriguez-Fdez, Kathleen Long, Ioannis Kamzolas, Sherine Awad, Dunja Lukovic, Slaven Erceg, Andrew Bassett, Sasha Mendjan, Ludovic Vallier, Barry S. Rosen, Davide Chiarugi, Antonio Vidal-Puig

The changing mouse embryo transcriptome at whole tissue and single-cell resolution
Peng He, Brian A. Williams, Diane Trout, Georgi K. Marinov, Henry Amrhein, Libera Berghella, Say-Tar Goh, Ingrid Plajzer-Frick, Veena Afzal, Len A. Pennacchio, Diane E. Dickel, Axel Visel, Bing Ren, Ross C. Hardison, Yu Zhang, Barbara J. Wold

Molecular architecture of the developing mouse brain
Gioele La Manno, Kimberly Siletti, Alessandro Furlan, Daniel Gyllborg, Elin Vinsland, Christoffer Mattsson Langseth, Irina Khven, Anna Johnsson, Mats Nilsson, Peter Lönnerberg, Sten Linnarsson

Molecular Logic of Cellular Diversification in the Mammalian Cerebral Cortex
Daniela J. Di Bella, Ehsan Habibi, Sun-Ming Yang, Robert R. Stickels, Juliana Brown, Payman Yadollahpour, Fei Chen, Evan Z. Macosko, Aviv Regev, Paola Arlotta

Single-nucleus transcriptomics reveals functional compartmentalization in syncytial skeletal muscle cells
Minchul Kim, Vedran Franke, Bettina Brandt, Elijah D. Lowenstein, Verena Schöwel, Simone Spuler, Altuna Akalin, Carmen Birchmeier

Systematic investigation of imprinted gene expression and enrichment in the mouse brain explored at single-cell resolution
M. J. Higgs, M. J. Hill, R. M. John, A. R. Isles

Ventricular, atrial and outflow tract heart progenitors arise from spatially and molecularly distinct regions of the primitive streak
Kenzo Ivanovitch, Pablo Soro-Barrio, Probir Chakravarty, Rebecca A Jones, S. Neda Mousavy Gharavy, Despina Stamataki, Julien Delile, James C Smith, James Briscoe

Chromatin topology and the timing of enhancer function at the hoxd locus
Eddie Rodríguez-Carballo, Lucille Lopez-Delisle, Andréa Willemin, Leonardo Beccari, Sandra Gitto, Bénédicte Mascrez, Denis Duboule

Subcellular mRNA localization and local translation of Arhgap11a in radial glial cells regulates cortical development
Louis-Jan Pilaz, Kaumudi Joshi, Jing Liu, Yuji Tsunekawa, Fernando C. Alsina, Sahil Sethi, Ikuo K. Suzuki, Pierre Vanderhaeghen, Franck Polleux, Debra L. Silver

RUNX1 marks a luminal castration resistant lineage established at the onset of prostate development
Renaud Mevel, Ivana Steiner, Susan Mason, Laura Galbraith, Rahima Patel, Muhammad ZH Fadlullah, Imran Ahmad, Hing Y. Leung, Pedro Oliveira, Karen Blyth, Esther Baena, Georges Lacaud

Pdgfra and Pdgfrb genetically interact in the murine neural crest cell lineage to regulate migration and proliferation
Julia Mo, Robert Long, Katherine A. Fantauzzo

Tet1 isoforms differentially regulate gene expression, synaptic transmission and memory in the mammalian brain
C.B. Greer, J. Wright, J.D. Weiss, R.M. Lazerenko, S.P. Moran, J. Zhu, K.S. Chronister, A.Y. Jin, A.J. Kennedy, J.D. Sweatt, G.A. Kaas

Laminin N-terminus α31 expression during development in an inducible-transgenic mouse model is lethal and causes a multitude of tissue-specific defects
Conor J. Sugden, Valentina Iorio, Lee D. Troughton, Ke Liu, George Bou-Gharios, Kevin J. Hamill

The long non-coding RNA Pax6os1/PAX6-AS1 modulates pancreatic β-cell identity and function
Livia Lopez-Noriega, Rebecca Callingham, Aida Martinez-Sánchez, Grazia Pizza, Nejc Haberman, Nevena Cvetesic, Boris Lenhard, Piero Marchetti, Lorenzo Piemonti, Eelco de Koning, A. M. James Shapiro, Paul R. Johnson, Isabelle Leclerc, Timothy J. Pullen, Guy A. Rutter

ESRP1-Mediated Alternative Splicing During Oocyte Development is Required for Mouse Fertility
Luping Yu, Huiru Zhang, Xuebing Guan, Dongdong Qin, Jian Zhou, Xin Wu

Polycomb-mediated Genome Architecture Enables Long-range Spreading of H3K27 methylation
Katerina Kraft, Kathryn E. Yost, Sedona Murphy, Andreas Magg, Yicheng Long, M.Ryan Corces, Jeffrey M. Granja, Stefan Mundlos, Thomas R. Cech, Alistair Boettiger, Howard Y. Chang

Genotypic Complexity in Initial Cleavage Divisions of Mammalian Embryos is Contributed by Defective BUB1B/BUBR1 Signaling
Kelsey E. Brooks, Brittany L. Daughtry, Brett Davis, Melissa Y. Yan, Suzanne S. Fei, Lucia Carbone, Shawn L. Chavez

Post-mitotic Prox1 expression controls the final specification of cortical VIP interneuron subtypes
Tevye Jason Stachniak, Rahel Kastli, Olivia Hanley, Ali Özgür Argunsah, Theofanis Karayannis

The Splicing Factor XAB2 interacts with ERCC1-XPF and XPG for RNA-loop processing during mammalian development
Evi Goulielmaki, Maria Tsekrekou, Nikos Batsiotos, Mariana Ascensão-Ferreira, Eleftheria Ledaki, Kalliopi Stratigi, Georgia Chatzinikolaou, Pantelis Topalis, Theodore Kosteas, Janine Altmüller, Jeroen A. Demmers, Nuno L. Barbosa-Morais, George A. Garinis

microRNAs (miR 9, 124, 155 and 224) transdifferentiate macrophages to neurons
Naveen Challagundla, Reena Agrawal-Rajput

miR6236, a microRNA suppressed by the anisotropic surface topography, regulates neuronal development and regeneration
Yi-Ju Chen, Yung-An Huang, Chris T. Ho, Jinn-Moon Yang, Jui-I Chao, Ming-Chia Li, Eric Hwang

Three Dimensional Multi-gene Expression Maps Reveal Cell Fate Changes Associated with Laterality Reversal of Zebrafish Habenula
Guo-Tzau Wang, He-Yen Pan, Wei-Han Lang, Yuan-Ding Yu, Chang-Huain Hsieh, Yung-Shu Kuan

Analysis of gene network bifurcation during optic cup morphogenesis in zebrafish
Lorena Buono, Silvia Naranjo, Tania Moreno-Marmol, Berta de la Cerda, Rocío Polvillo, Francisco-Javier Díaz-Corrales, Ozren Bogdanovic, Paola Bovolenta, Juan-Ramón Martínez-Morales

Overlapping and non-overlapping roles of the class-I histone deacetylase-1 corepressors, LET-418, SIN-3, and SPR-1 in Caenorhabditis elegans embryonic development
Yukihiro Kubota, Yuto Ohnishi, Tasuku Hamasaki, Gen Yasui, Natsumi Ota, Hiromu Kitagawa, Arashi Esaki, Muhamad Fahmi, Masahiro Ito

Single-Cell Protein Atlas of Transcription Factors Reveals the Combinatorial Code for Spatiotemporal Patterning the C. elegans Embryo
Xuehua Ma, Zhiguang Zhao, Long Xiao, Weina Xu, Yangyang Wang, Yanping Zhang, Gang Wu, Zhuo Du

Parallel genetics of regulatory sequences in vivo
Jonathan Froehlich, Bora Uyar, Margareta Herzog, Kathrin Theil, Petar Glažar, Altuna Akalin, Nikolaus Rajewsky

The pioneer factor GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo
Marissa M. Gaskill, Tyler J. Gibson, Elizabeth D. Larson, Melissa M. Harrison

A multi-informatic description of neural differentiation in the Drosophila type-II neuroblast lineages
Nigel S. Michki, Ye Li, Kayvon Sanjasaz, Yimeng Zhao, Fred Y. Shen, Logan A. Walker, Cheng-Yu Lee, Dawen Cai

Single cell visualisation of mir-9a and Senseless co-expression during Drosophila melanogaster embryonic and larval peripheral nervous system development
Lorenzo Gallicchio, Sam Griffiths-Jones, Matthew Ronshaugen

RNA degradation sculpts the maternal transcriptome during Drosophila oogenesis
Patrick Blatt, Siu Wah Wong-Deyrup, Alicia McCarthy, Shane Breznak, Matthew D. Hurton, Maitreyi Upadhyay, Benjamin Bennink, Justin Camacho, Miler T. Lee, Prashanth Rangan

Drosophila p53 isoforms have overlapping and distinct functions in germline genome integrity and oocyte quality control
Ananya Chakravarti, Heshani N. Thirimanne, Brian R. Calvi

The Drosophila MOZ homolog Enok controls Notch-dependent induction of the RUNX gene lozenge independently of its histone-acetyl transferase activity
Thomas Genais, Delhia Gigan, Benoit Augé, Douaa Moussalem, Lucas Waltzer, Marc Haenlin, Vanessa Gobert

| Stem cells, regeneration & disease modelling

Hoxa10 mediates positional memory to govern stem cell function in adult skeletal muscle
Kiyoshi Yoshioka, Hiroshi Nagahisa, Fumihito Miura, Hiromitsu Araki, Yasutomi Kamei, Yasuo Kitajima, Daiki Seko, Jumpei Nogami, Yoshifumi Tsuchiya, Narihiro Okazaki, Akihiko Yonekura, Seigo Ohba, Yoshinori Sumita, Ko Chiba, Kosei Ito, Izumi Asahina, Yoshihiro Ogawa, Takashi Ito, Yasuyuki Ohkawa, Yusuke Ono

Mitochondrial STAT3 regulates proliferation of tissue stem cells
Margherita Peron, Giacomo Meneghetti, Alberto Dinarello, Laura Martorano, Riccardo M. Betto, Nicola Facchinello, Natascia Tiso, Graziano Martello, Francesco Argenton

Cullin3 promotes stem cell progeny differentiation by facilitating aPKC-directed asymmetric Numb localization
Hideyuki Komori, Noemi Rives-Quinto, Xu Han, Lucas Anhezini, Ari J. Esrig, James B. Skeath, Cheng-Yu Lee

Endogenous suppression of WNT signalling in human embryonic stem cells leads to low differentiation propensity towards definitive endoderm
Dominika Dziedzicka, Mukul Tewary, Alexander Keller, Laurentijn Tilleman, Laura Prochazka, Joel Östblom, Edouard Couvreu De Deckersberg, Christina Markouli, Silvie Franck, Filip Van Nieuwerburgh, Claudia Spits, Peter W. Zandstra, Karen Sermon, Mieke Geens

Repopulating Kupffer Cells Originate Directly from Hematopoietic Stem Cells
Ying Jiang, Xu Fan, Pei Lu, Xianghua Cui, Peng Wu, Weiran Lin, Dong Zhang, Shongzong Yuan, Bing Liu, Fangyan Chen, Hong You, Handong Wei, Fuchu He, Jidong Jia

Capturing limbal epithelial stem cell population dynamics, signature, and their niche
Anna Altshuler, Aya Amitai-Lange, Noam Tarazi, Sunanda Dey, Lior Strinkovsky, Swarnabh Bhattacharya, Shira Hadad-Porat, Waseem Nasser, Jusuf Imeri, Gil Ben-David, Beatrice Tiosano, Eran Berkowitz, Nathan Karin, Yonatan Savir, Ruby Shalom-Feuerstein

NODAL/TGFβ signalling mediates the self-sustained stemness induced by PIK3CAH1047R homozygosity in pluripotent stem cells
Ralitsa R. Madsen, James Longden, Rachel G. Knox, Xavier Robin, Franziska Völlmy, Kenneth G. Macleod, Larissa S. Moniz, Neil O. Carragher, Rune Linding, Bart Vanhaesebroeck, Robert K. Semple

Ontogenic Shifts in Cellular Fate Are Linked to Proteotype Changes in Mouse Hematopoietic Progenitor Cells
Maria Jassinskaja, Kristýna Pimková, Emil Johansson, Ewa Sitnicka, Jenny Hansson

Dynamic spatiotemporal coordination of neural stem cell fate decisions through local feedback in the adult vertebrate brain
Nicolas Dray, Laure Mancini, Udi Binshtok, Felix Cheysson, Willy Supatto, Pierre Mahou, Sébastien Bedu, Sara Ortica, Monika Krecsmarik, Sébastien Herbert, Jean-Baptiste Masson, Jean-Yves Tinevez, Gabriel Lang, Emmanuel Beaurepaire, David Sprinzak, Laure Bally-Cuif

Phosphatidylinositol-3 kinase activity controls survival and stemness of zebrafish hematopoietic stem/progenitor cells
Sasja Blokzijl-Franke, Bas Ponsioen, Stefan Schulte-Merker, Philippe Herbomel, Karima Kissa, Suma Choorapoikayil, Jeroen den Hertog

Wnt- and Glutamate-receptors orchestrate stem cell dynamics and asymmetric cell division
Sergi Junyent, Joshua Reeves, James L. A. Szczerkowski, Clare L. Garcin, Tung-Jui Trieu, Matthew Wilson, Shukry J. Habib

Activation of a neural stem cell transcriptional program in parenchymal astrocytes
Jens P. Magnusson, Margherita Zamboni, Giuseppe Santopolo, Jeff E. Mold, Mauricio Barrientos-Somarribas, Carlos Talavera-López, Björn Andersson, Jonas Frisén

Loss of Nupr1 promotes engraftment by tuning the dormancy threshold of hematopoietic stem cell repository via regulating p53-checkpoint pathway
Tongjie Wang, Chengxiang Xia, Hui Cheng, Qitong Weng, Kaitao Wang, Yong Dong, Sha Hao, Fang Dong, Xiaofei Liu, Lijuan Liu, Yang Geng, Yuxian Guan, Juan Du, Tao Cheng, Jinyong Wang

Two DNA binding domains of Mga act in combination to suppress ectopic activation of meiosis-related genes in mouse embryonic stem cells
Kousuke Uranishi, Masataka Hirasaki, Yuka Kitamura, Yosuke Mizuno, Masazumi Nishimoto, Ayumu Suzuki, Akihiko Okuda

Mtg16-dependent repression of E protein activity is required for early lymphopoiesis
Pankaj Acharya, Shilpa Sampathi, David K. Flaherty, Brittany K. Matlock, Christopher S. Williams, Scott W. Hiebert, Kristy R. Stengel

Transcriptomic Profiling of Human Pluripotent Stem Cell-Derived Retinal Pigment Epithelium Over Time
Grace E. Lidgerwood, Anne Senabouth, Casey J.A. Smith-Anttila, Vikkitharan Gnanasambandapillai, Dominik C. Kaczorowski, Daniela Amann-Zalcenstein, Erica L. Fletcher, Shalin H. Naik, Alex W. Hewitt, Joseph E. Powell, Alice Pébay

High resolution mouse subventricular zone stem cell niche transcriptome reveals features of lineage, anatomy, and aging
Xuanhua P. Xie, Dan R. Laks, Daochun Sun, Asaf Poran, Ashley M. Laughney, Zilai Wang, Jessica Sam, German Belenguer, Isabel Fariñas, Olivier Elemento, Xiuping Zhou, Luis F. Parada

Long-term Reconstruction of Human Airway Epithelium-like Structure in Vivo with hESCs-derived organoid cells
Yong Chen, Le Han, Shanshan Zhao, Jianqi Feng, Lian Li, Zhili Rong, Ying Lin

Regeneration of Functional Retinal Ganglion Cells by Neuronal Identity Reprogramming
Xiaohu Wei, Zhenhao Zhang, Huan-huan Zeng, Xue-Feng Wang, Wenrong Zhan, Na Qiao, Zhen Chang, Lu Liu, Chengyu Fan, Ziwei Yang, Xiaoming Li, Yang Yang, Hongjun Liu

Primate heart regeneration via migration and fibroblast repulsion by human heart progenitors
Christine Schneider, Kylie S. Foo, Maria Teresa De Angelis, Gianluca Santamaria, Franziska Reiter, Tatjana Dorn, Andrea Bähr, Yat Long Tsoi, Petra Hoppmann, Ilaria My, Anna Meier, Victoria Jurisch, Nadja Hornaschewitz, Sascha Schwarz, Kun Lu, Roland Tomasi, Stefanie Sudhop, Elvira Parrotta, Marco Gaspari, Giovanni Cuda, Nikolai Klymiuk, Andreas Dendorfer, Markus Krane, Christian Kupatt, Daniel Sinnecker, Alessandra Moretti, Kenneth R. Chien, Karl-Ludwig Laugwitz

Neutrophil extracellular traps impair regeneration
Eric Wier, Mayumi Asada, Gaofeng Wang, Martin P. Alphonse, Ang Li, Chase Hintelmann, Christine Youn, Brittany Pielstick, Roger Ortines, Lloyd S. Miller, Nathan K. Archer, Luis A. Garza

Oral Regeneration Is the Default Pathway Triggered by Injury in Hydra
Jack Cazet, Celina Juliano

MAPK signaling links the injury response to Wnt-regulated patterning in Hydra regeneration
Anja Tursch, Natascha Bartsch, Thomas W. Holstein

Epigenetic immune-modulation by Histone Deacetylase Activity (HDAC) of tissue and organ regeneration in Xenopus laevis
Nathalia Pentagna, Felipe Soares dos Santos, Fernanda Martins de Almeida, José Garcia Abreu, Michael Levin, Katia Carneiro

TRANsCre-DIONE transdifferentiates scar-forming reactive astrocytes into functional motor neurons
Heeyoung An, Hye-Lan Lee, Doo-Wan Cho, Jinpyo Hong, Hye Yeong Lee, Jung Moo Lee, Junsung Woo, Jaekwang Lee, MinGu Park, Young-Su Yang, Su-Cheol Han, Yoon Ha, C. Justin Lee

Genome-Scale CRISPR Screening reveals novel factors regulating Wnt-dependent regeneration of mouse gastric organoids
Kazuhiro Murakami, Yumi Terakado, Kikue Saito, Yoshie Jomen, Haruna Takeda, Masanobu Oshima, Nick Barker

Mechanical overstimulation causes acute injury followed by fast recovery in lateral-line neuromasts of larval zebrafish
Melanie Holmgren, Michael E. Ravicz, Kenneth E. Hancock, Olga Strelkova, Artur A. Indzhykulian, Mark E. Warchol, Lavinia Sheets

Disruption of a Hedgehog-Foxf1-Rspo2 Signaling Axis Leads to Tracheomalacia and a Loss of Sox9+ Tracheal Chondrocytes
Talia Nasr, Praneet Chaturvedi, Kunal Agarwal, Jessica L. Kinney, Keziah Daniels, Stephen L. Trisno, Vladimir Ustiyan, John M. Shannon, James M. Wells, Debora Sinner, Vladimir V. Kalinichenko, Aaron M. Zorn

Human iPSC-based neurodevelopmental models of globoid cell leukodystrophy uncover patient- and cell type-specific disease phenotypes
Elisabeth Mangiameli, Anna Cecchele, Francesco Morena, Francesca Sanvito, Vittoria Matafora, Angela Cattaneo, Lucrezia Della Volpe, Daniela Gnani, Marianna Paulis, Lucia Susani, Sabata Martino, Raffaella Di Micco, Angela Bachi, Angela Gritti

Altered vertebrae morphology and bone mineralization in a zebrafish model of CHARGE syndrome
Maximilian Breuer, Maximilian Rummler, Charlotte Zaouter, Bettina M. Willie, Shunmoogum A. Patten

Structural engraftment and topographic spacing of transplanted human stem cell-derived retinal ganglion cells
Kevin Y Zhang, Caitlyn Tuffy, Joseph L Mertz, Sarah Quillen, Laurence Wechsler, Harry A Quigley, Donald J Zack, Thomas V Johnson

Wide phenotypic spectrum of human stem cell-derived excitatory neurons with Rett syndrome-associated MECP2 mutations
Rebecca SF Mok, Wenbo Zhang, Taimoor I Sheikh, Isabella R Fernandes, Leah C DeJong, Matthew R Hildebrandt, Marat Mufteev, Deivid C Rodrigues, Wei Wei, Alina Piekna, Jiaje Liu, Alysson R Muotri, John B Vincent, Michael W Salter, James Ellis

Human embryonic stem cells-derived dopaminergic neurons transplanted in parkinsonian monkeys recover dopamine levels and motor behavior
Adolfo López-Ornelas, Itzel Escobedo-Avila, Gabriel Ramírez-García, Rolando Lara-Rodarte, César Meléndez-Ramírez, Beetsi Urrieta-Chávez, Tonatiuh Barrios-García, Verónica A. Cáceres-Chávez, Xóchitl Flores-Ponce, Francia Carmona, Carlos Alberto Reynoso, Carlos Aguilar, Nora E. Kerik, Luisa Rocha, Leticia Verdugo-Díaz, Víctor Treviño, José Bargas, Verónica Ramos-Mejía, Juan Fernández-Ruiz, Aurelio Campos-Romo, Iván Velasco

Autism-linked Cullin3 germline haploinsufficiency impacts cytoskeletal dynamics and cortical neurogenesis through RhoA signaling
Megha Amar, Akula Bala Pramod, Nam-Kyung Yu, Victor Munive Herrera, Lily R. Qiu, Patricia Moran-Losada, Pan Zhang, Cleber A. Trujillo, Jacob Ellegood, Jorge Urresti, Kevin Chau, Jolene Diedrich, Jiaye Chen, Jessica Gutierrez, Jonathan Sebat, Dhakshin Ramanathan, Jason P. Lerch, John R. Yates III, Alysson R. Muotri, Lilia M. Iakoucheva

Neurodegeneration induces a developmental RNA processing program by calpain-mediated MBNL2 degradation
Lee-Hsin Wang, Yu-Mei Lin, Chien-Yu Lin, Yijuang Chern, Guey-Shin Wang

Assessment of autism zebrafish mutant models using a high-throughput larval phenotyping platform
Alexandra Colón-Rodríguez, José M. Uribe-Salazar, KaeChandra B. Weyenberg, Aditya Sriram, Alejandra Quezada, Gulhan Kaya, Emily Jao, Brittany Radke, Pamela J. Lein, Megan Y. Dennis

A zebrafish model of Granulin deficiency reveals essential roles in myeloid cell differentiation
Clyde A. Campbell, Oksana Fursova, Xiaoyi Cheng, Elizabeth Snella, Abbigail McCune, Liangdao Li, Barbara Solchenberger, Bettina Schmid, Debashis Sahoo, Mark Morton, David Traver, Raquel Espín-Palazón

RHEB/mTOR-hyperactivity causing cortical malformations drives seizures through increased axonal connectivity
Martina Proietti Onori, Linda M.C. Koene, Carmen B. Schafer, Mark Nellist, Marcel de Brito van Velze, Zhenyu Gao, Ype Elgersma, Geeske M. van Woerden

| Plant development

Altered stomatal patterning accompanies a trichome dimorphism in a natural population of Arabidopsis
Noriane M. L. Simon, Jiro Sugisaka, Mie N. Honjo, Sverre Aarseth Tunstad, George Tunna, Hiroshi Kudoh, Antony N. Dodd

Precise transcriptional control of cellular quiescence by BRAVO/WOX5 complex in Arabidopsis roots
Isabel Betegón-Putze, Josep Mercadal, Nadja Bosch, Ainoa Planas-Riverola, Mar Marquès-Bueno, Josep Vilarrasa-Blasi, David Frigola, Rebecca Corinna Burkart, Cristina Martínez, Yvonne Stahl, Salomé Prat, Marta Ibañes, Ana I. Caño-Delgado

Expansin-controlled cell wall stiffness regulates root growth in Arabidopsis
Marketa Samalova, Kareem Elsayad, Alesia Melnikava, Alexis Peaucelle, Evelina Gahurova, Jaromir Gumulec, Ioannis Spyroglou, Elena V. Zemlyanskaya, Elena V. Ubogoeva, Jan Hejatko

Root electrotropism in Arabidopsis does not depend on auxin distribution, requires cytokinin biosynthesis and follows a power-law response curve
Nicholas Oliver, Maddalena Salvalaio, Deniz Tiknaz, Maximillian Schwarze, Nicolas Kral, Soo-Jeong Kim, Giovanni Sena

The IncRNA APOLO interacts with the transcription factor WRKY42 to trigger root hair cell expansion in response to cold
Michaël Moison, Javier Martínez Pacheco, Leandro Lucero, Camille Fonouni-Farde, Johan Rodríguez-Melo, Aurélie Christ, Jérémie Bazin, Moussa Benhamed, Fernando Ibañez, Martin Crespi, José M. Estevez, Federico Ariel

ABCB-mediated auxin transport in outer root tissues regulates lateral root spacing in Arabidopsis
Jian Chen, Yangjie Hu, Pengchao Hao, Yuqin Zhang, Ohad Roth, Maria F. Njo, Lieven Sterck, Yun Hu, Yunde Zhao, Markus Geisler, Eilon Shani, Tom Beeckman, Steffen Vanneste

The PIF1-MIR408-Plantacyanin Repression Cascade Regulates Light Dependent Seed Germination
Anlong Jiang, Zhonglong Guo, Jiawei Pan, Yan Zhuang, Daqing Zuo, Chen Hao, Zhaoxu Gao, Peiyong Xin, Jinfang Chu, Shangwei Zhong, Lei Li

Temperature-dependent fasciation mutants connect mitochondrial RNA processing to the control of cell proliferation during lateral root morphogenesis
Kurataka Otsuka, Akihito Mamiya, Mineko Konishi, Mamoru Nozaki, Atsuko Kinoshita, Hiroaki Tamaki, Masaki Arita, Masato Saito, Kayoko Yamamoto, Takushi Hachiya, Ko Noguchi, Takashi Ueda, Yusuke Yagi, Takehito Kobayashi, Takahiro Nakamura, Yasushi Sato, Takashi Hirayama, Munetaka Sugiyama

High-resolution temporal transcript profiling during Arabidopsis thaliana gynoecium morphogenesis uncovers the chronology of gene regulatory network activity and reveals novel developmental regulators
Kimmo I. Kivivirta, Denise Herbert, Clemens Roessner, Stefan de Folter, Nayelli Marsch-Martinez, Annette Becker

Developmental constraints modulate reproductive fate and plasticity within the Arabidopsis ovule primordium
Elvira Hernandez-Lagana, Gabriella Mosca, Ethel Mendocilla Sato, Nuno Pires, Anja Frey, Alejandro Giraldo-Fonseca, Ueli Grossniklaus, Olivier Hamant, Christophe Godin, Arezki Boudaoud, Daniel Grimanelli, Daphné Autran, Célia Baroux

SUMOylation contributes to proteostasis of the chloroplast protein import receptor TOC159 during early development
Sonia Accossato, Felix Kessler, Venkatasalam Shanmugabalaji

The impact of chromatin remodeling on gene expression at the single cell level in Arabidopsis thaliana
Andrew Farmer, Sandra Thibivilliers, Kook Hui Ryu, John Schiefelbein, Marc Libault

H3.1K27me1 maintains transcriptional silencing and genome stability by preventing GCN5-mediated histone acetylation
Jie Dong, Chantal LeBlanc, Axel Poulet, Benoit Mermaz, Gonzalo Villarino, Kimberly M. Webb, Valentin Joly, Josefina Mendez, Philipp Voigt, Yannick Jacob

NO GAMETOPHORES 2 is a novel regulator of the 2D to 3D growth transition in the moss Physcomitrium patens
Laura A. Moody, Steven Kelly, Roxaana Clayton, Zoe Weeks, David M. Emms, Jane A. Langdale

Underground gibberellin activity: differential gibberellin response in tomato shoots and roots
Uria Ramon, David Weiss, Natanella Illouz-Eliaz

Phytochromes B1/B2 are major regulators of ripening-associated epigenome reprogramming in tomato fruits
Ricardo Bianchetti, Nicolas Bellora, Luis A de Haro, Rafael Zuccarelli, Daniele Rosado, Luciano Freschi, Magdalena Rossi, Luisa Bermudez

Organogenesis and Vasculature of Anaxagorea and its Implications in the Integrated Axial-Foliar Origin of the Angiosperm Carpel
Ya Li, Wei Du, Shuai Wang, Xiao-Fan Wang

Fruit presence induces polar auxin transport in citrus and olive stem and represses hormone release from the bud
Dor Haim, Liron Shalom, Yasmin Simhon, Lyudmila Shlizerman, Itzhak Kamara, Michael Morozov, Alfonso Ant Albacete Moreo, Rosa M Rivero, Avi Sadka

Fine tuning of hormonal signaling is linked to dormancy status in sweet cherry flower buds
Noémie Vimont, Adrian Schwarzenberg, Mirela Domijan, Armel S. L. Donkpegan, Rémi Beauvieux, Loïck le Dantec, Mustapha Arkoun, Frank Jamois, Jean-Claude Yvin, Philip A. Wig

INTERMEDIUM-C mediates the shade-induced bud growth arrest in barley
Hongwen Wang, Christiane Seiler, Nese Sreenivasulu, Nicolaus von Wirén, Markus Kuhlmann

Evo-devo & evo

Developmental, cellular, and biochemical basis of transparency in the glasswing butterfly Greta oto
Aaron F. Pomerantz, Radwanul H. Siddique, Elizabeth I. Cash, Yuriko Kishi, Charline Pinna, Kasia Hammar, Doris Gomez, Marianne Elias, Nipam H. Patel

Acoel single-cell transcriptomics: cell-type analysis of a deep branching bilaterian
Jules Duruz, Cyrielle Kaltenrieder, Peter Ladurner, Rémy Bruggmann, Pedro Martìnez, Simon G. Sprecher

Muscle cell type diversification facilitated by extensive gene duplications
Alison G. Cole, Sabrina Kaul, Stefan M. Jahnel, Julia Steger, Bob Zimmerman, Robert Reischl, Gemma Sian Richards, Fabian Rentzsch, Patrick Steinmetz, Ulrich Technau

Embryonic origin and serial homology of gill arches and paired fins in the skate (Leucoraja erinacea)
Victoria A. Sleight, J. Andrew Gillis

Single-cell morphometrics reveals ancestral principles of notochord development
Toby G R Andrews, Wolfram Pönisch, Ewa Paluch, Benjamin J Steventon, Elia Benito-Gutierrez

The evolution of Sox gene repertoires and regulation of segmentation in arachnids
Luis Baudouin-Gonzalez, Anna Schoenauer, Amber Harper, Grace Blakeley, Michael Seiter, Saad Arif, Lauren Sumner-Rooney, Steven Russell, Prashant P. Sharma, Alistair P. McGregor

Widespread retention of ohnologs in key developmental gene families following whole genome duplication in arachnopulmonates
Amber Harper, Luis Baudouin Gonzalez, Anna Schönauer, Michael Seiter, Michaela Holzem, Saad Arif, Alistair P. McGregor, Lauren Sumner-Rooney

The developmental and genetic architecture of the sexually selected male ornament of swordtails
Manfred Schartl, Susanne Kneitz, Jenny Ormanns, Cornelia Schmidt, Jennifer L Anderson, Angel Amores, Julian Catchen, Catherine Wilson, Dietmar Geiger, Kang Du, Mateo Garcia-Olazábal, Sudha Sudaram, Christoph Winkler, Rainer Hedrich, Wesley C Warren, Ronald Walter, Axel Meyer, John H Postlethwait

An early cell shape transition drives evolutionary expansion of the human forebrain
Silvia Benito-Kwiecinski, Stefano L. Giandomenico, Magdalena Sutcliffe, Erlend S. Riis, Paula Freire-Pritchett, Iva Kelava, Stephanie Wunderlich, Ulrich Martin, Greg Wray, Madeline A. Lancaster

Mitochondrial state determines functionally divergent stem cell population in planaria
Mohamed Mohamed Haroon, Vairavan Lakshmanan, Souradeep R. Sarkar, Kai Lei, Praveen Kumar Vemula, Dasaradhi Palakodeti

The essential role of Dnmt1 in gametogenesis in the large milkweed bug Oncopeltus fasciatus
Joshua T. Washington, Katelyn R. Cavender, Ashley U. Amukamara, Elizabeth C. McKinney, Robert J. Schmitz, Patricia J. Moore

The direct regulation of Aalbdsx on AalVgR is indispensable for ovarian development in Aedes albopictus
Binbin Jin, Yijie Zhao, Peiwen Liu, Yan Sun, Xiaocong Li, Xin Zhang, Xiao-Guang Chen, Jinbao Gu

Differences in developmental potential predict the contrasting patterns of dental diversification in characiform and cypriniform fishes
David Jandzik, David W Stock

Evolution of regulatory signatures in primate cortical neurons at cell type resolution
Alexey Kozlenkov, Marit W. Vermunt, Pasha Apontes, Junhao Li, Ke Hao, Chet C. Sherwood, Patrick R. Hof, John J. Ely, Michael Wegner, Eran A. Mukamel, Menno P. Creyghton, Eugene V. Koonin, Stella Dracheva

Testing for a role of Dnmt2 in paternal trans-generational immune priming
Nora K E Schulz, Maike F Diddens-de Buhr, Joachim Kurtz

Balancing selection maintains ancient genetic diversity in C. elegans
Daehan Lee, Stefan Zdraljevic, Lewis Stevens, Ye Wang, Robyn E. Tanny, Timothy A. Crombie, Daniel E. Cook, Amy K. Webster, Rojin Chirakar, L. Ryan Baugh, Mark G. Sterken, Christian Braendle, Marie-Anne Félix, Matthew V. Rockman, Erik C. Andersen

Inferring the genetic basis of sex determination from the genome of a dioecious nightshade
Meng Wu, Gregory J. Anderson, Matthew W. Hahn, Leonie C. Moyle, Rafael F. Guerrero

Lack of support for Deuterostomia prompts reinterpretation of the first Bilateria
Paschalia Kapli, Paschalis Natsidis, Daniel J. Leite, Maximilian Fursman, Nadia Jeffrie, Imran A. Rahman, Hervé Philippe, Richard R. Copley, Maximilian J. Telford

Cell biology

Sister chromatid repair maintains genomic integrity during meiosis in Caenorhabditis elegans
Erik Toraason, Cordell Clark, Anna Horacek, Marissa L. Glover, Alina Salagean, Diana E. Libuda

Meiotic sister chromatid exchanges are rare in C. elegans
David E. Almanzar, Spencer G. Gordon, Ofer Rog

The Nesprin-1/-2 ortholog ANC-1 regulates organelle positioning in C. elegans without its KASH or actin-binding domains
Hongyan Hao, Shilpi Kalra, Laura E. Jameson, Leslie A. Guerrero, Natalie E. Cain, Jessica Bolivar, Daniel A. Starr

Phosphoregulation of HORMA domain protein HIM-3 promotes asymmetric synaptonemal complex disassembly in meiotic prophase in C. elegans
Aya Sato-Carlton, Chihiro Nakamura-Tabuchi, Xuan Li, Hendrik Boog, Madison K Lehmer, Scott C Rosenberg, Consuelo Barroso, Enrique Martinez-Perez, Kevin D Corbett, Peter Mark Carlton

FLN-1/Filamin is required to anchor the actomyosin cytoskeleton and for global organization of sub-cellular organelles in a contractile tissue
Charlotte A. Kelley, Olivia Triplett, Samyukta Mallick, Kristopher Burkewitz, William B. Mair, Erin J. Cram

Long-term live imaging of epithelial organoids and corresponding multiscale analysis reveal high heterogeneity and identify core regulatory principles
Lotta Hof, Till Moreth, Michael Koch, Tim Liebisch, Marina Kurtz, Julia Tarnick, Susanna M. Lissek, Monique M.A. Verstegen, Luc J.W. van der Laan, Meritxell Huch, Franziska Matthäus, Ernst H.K. Stelzer, Francesco Pampaloni

Combinatorial deployment of F-actin regulators to build complex 3D actin structures in vivo
Yi Xie, J. Todd Blankenship

The Drosophila EGFR ligand mSpitz is delivered to cytoplasmic capes at sites of non-canonical RNA export on the nuclear envelope via the endosomal system
Floyd J. Mattie, Praveen Kumar, Mark D. Travor, Kristen C. Browder, Claire M. Thomas

RhoA effectors LOK/SLK activate ERM proteins to locally inhibit RhoA and define apical morphology
Riasat Zaman, Andrew Lombardo, Cécile Sauvanet, Raghuvir Viswanatha, Valerie Awad, Locke Ezra-Ros Bonomo, David McDermitt, Anthony Bretscher

Time-resolved proteomic profiling of the ciliary Hedgehog response reveals that GPR161 and PKA undergo regulated co-exit from cilia
Elena A. May, Marian Kalocsay, Inès Galtier D’Auriac, Steven P. Gygi, Maxence V. Nachury, David U. Mick

Lamin C regulates genome organization after mitosis
X Wong, VE Hoskins, JC Harr, M Gordon, KL Reddy

Microtubules tune mechanosensitive cell responses
Shailaja Seetharaman, Benoit Vianay, Vanessa Roca, Chiara De Pascalis, Batiste Boëda, Florent Dingli, Damarys Loew, Stéphane Vassilopoulos, Manuel Théry, Sandrine Etienne-Manneville

Identification of a new regulation pathway of EGFR and E-cadherin dynamics
Veronique Proux-Gillardeaux, Tamara Advedissian, Charlotte Perin, Jean-Christophe Gelly, Mireille Viguier, Fredérique Deshayes

Modelling

Computational modelling unveils how epiblast remodelling and positioning rely on trophectoderm morphogenesis during mouse implantation
Joel Dokmegang, Moi Hoon Yap, Liangxiu Han, Matteo Cavaliere, René Doursat

Geometric models for robust encoding of dynamical information into embryonic patterns
Laurent Jutras-Dubé, Ezzat El-Sherif, Paul François

Cell-scale biophysical determinants of cell competition in epithelia
Daniel Gradeci, Anna Bove, Giulia Vallardi, Alan R. Lowe, Shiladitya Banerjee, Guillaume Charras

Size-regulated symmetry breaking in reaction-diffusion models of developmental transitions
Jake Cornwall Scoones, Deb Sankar Banerjee, Shiladitya Banerjee

A deep reinforcement learning model based on deterministic policy gradient for collective neural crest cell migration
Yihao Zhang, Zhaojie Chai, Yubing Sun, George Lykotrafitis

A hybrid discrete-continuum approach to model Turing pattern formation
Fiona R Macfarlane, Mark AJ Chaplain, Tommaso Lorenzi

Lineage optimization in nematode’s early embryogenesis
Guoye Guan, Ming-Kin Wong, Zhongying Zhao, Lei-Han Tang, Chao Tang

Modelling cellular signalling variability based on single-cell data: the TGFb/SMAD signaling pathway
Uddipan Sarma, Lorenz Hexemer, Uchenna Alex Anyaegbunam, Stefan Legewie

A free boundary mechanobiological model of epithelial tissues
Tamara A. Tambyah, Ryan J. Murphy, Pascal R. Buenzli, Matthew J. Simpson

Tools & resources

A new species of planarian flatworm from Mexico: Girardia guanajuatiensis
Elizabeth M. Duncan, Stephanie H. Nowotarski, Carlos Guerrero-Hernández, Eric J. Ross, Julia A. D’Orazio, Clubes de Ciencia México Workshop for Developmental Biology, Sean McKinney, Longhua Guo, Alejandro Sánchez Alvarado

Application of CRISPR/Cas9 nuclease in amphioxus genome editing
Liuru Su, Chenggang Shi, Xin Huang, Yiquan Wang, Guang Li

Lineage recording of zebrafish embryogenesis reveals historical and ongoing lineage commitments
Zhuoxin Chen, Chang Ye, Zhan Liu, Shanjun Deng, Xionglei He, Jin Xu

Endogenous zebrafish proneural Cre drivers generated by CRISPR/Cas9 short homology directed targeted integration
Maira P. Almeida, Jordan M. Welker, Stephen C. Ekker, Karl J. Clark, Jeffrey J. Essner, Maura McGrail

A CRISPR/Cas9 vector system for neutrophil-specific gene disruption in zebrafish
Yueyang Wang, Alan Y. Hsu, Eric M. Walton, Ramizah Syahirah, Tianqi Wang, Wenqing Zhou, Chang Ding, Abby Pei Lemke, David M. Tobin, Qing Deng

A deep learning approach for staging embryonic tissue isolates with small data
Adam Pond, Seongwon Hwang, Berta Verd, Benjamin Steventon

Dehydrated Caenorhabditis elegans stocks are resistant to multiple freeze-thaw cycles
Patrick D. McClanahan, Richard J. McCloskey, Melanie N. T. Hing, David M. Raizen, Christopher Fang-Yen

Adaptable and Efficient Genome Editing by sgRNA-Cas9 Protein Co-injection into Drosophila
Kevin G. Nyberg, Joseph Q. Nguyen, Yong-Jae Kwon, Shelby Blythe, Greg J. Beitel, Richard W. Carthew

AggreCount: An unbiased image analysis tool for identifying and quantifying cellular aggregates in a spatial manner
Jacob Aaron Klickstein, Sirisha Mukkavalli, Malavika Raman

Split-wrmScarlet and split-sfGFP: tools for faster, easier fluorescent labeling of endogenous proteins in Caenorhabditis elegans
Jérôme Goudeau, Jonathan Paw, Laura Savy, Manuel D. Leonetti, Andrew G. York, Cynthia Kenyon, Maria Ingaramo

Segmentation of the Zebrafish Brain Vasculature from Light Sheet Fluorescence Microscopy Datasets
Elisabeth C. Kugler, Andrik Rampun, Timothy J.A. Chico, Paul A. Armitage

Fluorescent in vivo editing reporter (FIVER): A novel multispectral reporter of in vivo genome editing
Peter A. Tennant, Robert G. Foster, Daniel O. Dodd, Ieng Fong Sou, Fraser McPhie, Nicholas Younger, Laura C. Murphy, Matthew Pearson, Bertrand Vernay, Margaret A. Keighren, Peter Budd, Stephen L. Hart, Roly Megaw, Luke Boulter, Pleasantine Mill

Rosa26 docking sites for investigating genetic circuit silencing in stem cells
Michael Fitzgerald, Mark Livingston, Chelsea Gibbs, Tara L. Deans

Upgraded CRISPR/Cas9 Tools for Tissue-Specific Mutagenesis in Drosophila
Gabriel T. Koreman, Qinan Hu, Yineng Xu, Zijing Zhang, Sarah E. Allen, Mariana F. Wolfner, Bei Wang, Chun Han

NeuroPAL: A Neuronal Polychromatic Atlas of Landmarks for Whole-Brain Imaging in C. elegans
Eviatar Yemini, Albert Lin, Amin Nejatbakhsh, Erdem Varol, Ruoxi Sun, Gonzalo E. Mena, Aravinthan D.T. Samuel, Liam Paninski, Vivek Venkatachalam, Oliver Hobert

A simple and highly efficient method for multi-allelic CRISPR-Cas9 editing in primary cell cultures
Pia Hoellerbauer, Megan Kufeld, Sonali Arora, Hua-Jun Wu, Heather M. Feldman, Patrick J. Paddison

Research practice & education

Gender, race and parenthood impact academic productivity during the COVID-19 pandemic: from survey to action
Fernanda Staniscuaski, Livia Kmetzsch, Eugenia Zandonà, Fernanda Reichert, Rossana C. Soletti, Zelia M.C Ludwig, Eliade F. Lima, Adriana Neumann, Ida V.D. Schwartz, Pamela B. Mello-Carpes, Alessandra S.K. Tamajusuku, Fernanda P. Werneck, Felipe K. Ricachenevsky, Camila Infanger, Adriana Seixas, Charley C. Staats, Leticia de Oliveira

Advancing science or advancing careers? Researchers’ opinions on success indicators
Noémie Aubert Bonn, Wim Pinxten

An integrated, modular approach to data science education in the life sciences
Kimberly A Dill-McFarland, Stephan G König, Florent Mazel, David Oliver, Lisa M McEwen, Kris Y Hong, Steven J Hallam

Examining gender imbalance in chemistry authorship
Adam D. Cotton, Ian B. Seiple

Only two out of five articles by New Zealand researchers are free-to-access: a multiple API study of access, its impact on open citation advantage, cost of Article Processing Charges (APC), and the potential to increase the proportion of open access
Richard Kenneth Alistair White, Anton Angelo, Deborah Jane Fitchett, Moira Fraser, Luqman Hayes, Jess Howie, Emma Richardson, Bruce Duncan White

A Multi-perspective Analysis of Retractions in Life Sciences
Bhumika Bhatt

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Two postdoc positions are available at the Laboratory of the Biochemistry of Cell Signalling, University of São Paulo’s Institute of Chemistry, Brazil.

The main goal of the laboratory is to understand the signaling pathways that lead to pain to guide the development of new non-opioid analgesics. We aim to study signaling pathways involved in the embryonic development of components of the pain system and the signal transduction processes involved in nociceptive pain mediated by Nerve Growth factor (NGF) and the kinase activated by this growth factor, TrkA.

In another subproject we study the role of the kinase PKMzeta in synaptic remodeling in chronic pain.

Requirements

The applicant should have obtained a PhD degree for less than seven years and be well acquainted with molecular and cell biology. As one of the projects focuses on Developmental Biology, previous experience in this field is desirable but not strictly necessary.

To apply, please submit applications to deborah@iq.usp.br including:

1) Academic curriculum, including contact information for 2-3 references;
2) Cover letter stating your aims and motivation for applying for the position.

Application deadline August 30, 2020.

This opportunity is open to candidates of any nationalities. The selected candidate will receive a FAPESP’s Post-Doctoral fellowship in the amount of R$ 7,373.10 monthly and a research contingency fund, equivalent to 15% of the annual value of the fellowship which should be spent in items directly related to the research activity.

Details regarding Postdoctoral fellowships by FAPESP can be found at http://www.fapesp.br/en/postdoc.

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A postdoctoral research position is available in the laboratory of Dr. Kristin Gribble at the Marine Biological Laboratory, Woods Hole, MA. The interests of the lab include the mechanisms and evolution of the biology of aging, and maternal and transgenerational effects on offspring health. We use rotifers as a model system for our work. For more information about our lab’s work and a list of publications, see mbl.edu/jbpc/gribble.

Qualified applicants will have the opportunity to study the genetic and epigenetic mechanisms of aging in a novel experimental model system, focusing on how maternal effects influence offspring health and lifespan. This NSF-CAREER funded research program will use experimental, genetic, biochemical, and bioinformatic approaches to elucidate the mechanisms of transgenerational epigenetic inheritance.

Applicants should posses a Ph.D. in molecular biology, cell biology, biochemistry, genetics, bioinformatics, or a related field.  The ideal candidate will have a record of scientific rigor, productivity, and creativity; the ability to work independently and as part of a team; and a strong publication record.  Excellent oral and written communication skills are required.  Highly motivated individuals with experience in other model systems and a background in biochemistry, cell/molecular biology, epigenetics, and/or bioinformatics are encouraged to apply. Salary will be commensurate with experience and qualifications.

Applicants must apply for this position via the Marine Biological Laboratory careers website. Please submit: a cover letter with a brief description of your research experience and how your expertise will contribute to research on the mechanisms of parental effects and transgenerational inheritance; a CV including a list of publications, and contact information for three references.

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The new Center for Stem Cell & Organoid Medicine (CuSTOM) at Cincinnati Children’s Hospital Medical Center (CCHMC) is launching a major new initiative to recruit outstanding tenure-track or tenured faculty at the Assistant to Associate Professor level.

CuSTOM (www.cincinnatichildrens.org/custom) is a multi-disciplinary center of excellence integrating developmental and stem cell biologists, clinicians, bioengineers and entrepreneurs with the common goal of accelerating discovery and facilitating bench-to-bedside translation of organoid technology and regenerative medicine. Faculty in CuSTOM benefit from the unique environment and resources to studies of human development, disease and regenerative medicine using pluripotent stem cell and organoid platforms.

CCHMC is a leader in organoid biology and one of the top ranked pediatric research centers in the world, providing a unique environment for basic and translational research. Among pediatric institutions CCHMC is the third-highest ranking recipient of research grants from the National Institutes of Health. CCHMC continues to make major investments in research supporting discovery with 1.4 million square feet of research space and subsidized state-of-the-art core facilities including a human pluripotent stem cell facility, CRISPR genome editing, high-throughput DNA analysis, biomedical informatics, a Nikon Center of Excellence imaging core and much more.

We invite applications from innovative and collaborative investigators focused on basic or translational research in human development and/or disease using stem cells or organoid models. Successful candidates must hold the PhD, MD, or MD/PhD degrees, and will have a vibrant research program with an outstanding publication record.

Applicants should submit their curriculum vitae, two to three page research statement focused on future plans, and contact information for three people who will provide letters of recommendation to CuSTOM@cchmc.org. Applications must be submitted by December 1st, 2020

The Cincinnati Children’s Hospital Medical Center, and the University of Cincinnati are Affirmative Action/Equal Opportunity Employers, fostering diversity and inclusion. Qualified women and minority candidates are especially encouraged to apply.

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In the latest episode of Genetics Unzipped, Kat Arney looks at the ancient war between our genes and the pathogens that infect us, going back thousands of years to the Black Death and before, through to our very latest foe: the SARS-CoV-2 coronavirus behind COVID-19.

With Claire Steves (King’s College London), Christiana Scheib (University of Tartu) and Lucy van Dorp (UCL).

Genetics Unzipped is the podcast from The Genetics Society. Full transcript, links and references available online at GeneticsUnzipped.com

Subscribe from Apple podcasts, Spotify, or wherever you get your podcasts.

And head over to GeneticsUnzipped.com to catch up on our extensive back catalogue.

If you enjoy the show, please do rate and review on Apple podcasts and help to spread the word on social media. And you can always send feedback and suggestions for future episodes and guests to podcast@geneticsunzipped.com Follow us on Twitter – @geneticsunzip

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By Michael Heide and Wieland B. Huttner

Introduction

The neocortex is the seat of our higher cognitive abilities that distinguish us from other mammals and that make us human (Rakic, 2009). One basis for this crucial feature is the increase in the size of the neocortex during hominin evolution, culminating in modern humans (Striedter, 2005, Azevedo et al., 2009, Kaas, 2013, Sousa et al., 2017, Molnar et al., 2019). A key issue in this context is the identification of genomic determinants that underlie the increased growth of the neocortex during brain development. Once candidate genes have been identified, the challenge then is to demonstrate their role in neocortex expansion in an appropriate system. Here, we summarize the background information that suggested the human-specific gene ARHGAP11B to be a candidate to have contributed to neocortex expansion and folding during human evolution, and explain the rationale for demonstrating this role in an ARHGAP11B-transgenic non-human primate model system, that is, fetuses of the common marmoset. Such functional, developmental and evolutionary studies have so far been rarely performed in transgenic non-human primates. In our recent publication, Heide et al. 2020, we show that the human-specific gene ARHGAP11B, when expressed to physiological levels in the fetal marmoset neocortex, indeed causes neocortex expansion and increases neocortex folding, implying that this gene significantly contributed to human neocortex evolution (Heide et al., 2020). Moreover, we hope that our findings provide evidence in support of the usefulness and feasibility of genetically modified non-human primates for neurodevelopmental and evolutionary studies, as well as other fields of neurobiology.

A need for genetically modifiable non-human primate models in neurobiological studies

Which systems are most appropriate for studying the development of the neocortex with the aim to gain insight into the development and evolution of the human neocortex? Commonly used animal models that lend themselves to genetic modifications have been smooth-brained (lissencephalic) rodents (mouse, rat) and the ferret, a carnivore with a folded (gyrencephalic) brain (Molnar et al., 2006, Sun and Hevner, 2014, Kawasaki, 2018, Zhao and Bhattacharyya, 2018). However, many findings about neocortical development obtained in these model systems cannot be translated as such to humans, as is exemplified, in particular, in the case of many mouse disease models (e.g., mouse models of primary microcephaly (Pinson et al., 2019)).

A recently emerged, promising in vitro model system of human neocortical development that overcomes some of these limitations are human brain organoids (Kadoshima et al., 2013, Lancaster et al., 2013, Camp et al., 2015, Qian et al., 2016, Quadrato et al., 2017). These are 3D cellular assemblies that model the tissue of certain brain regions over a particular developmental time window and recapitulate many aspects of the cytoarchitecture and cell-type complexity of the modelled brain tissue (Heide et al., 2018). Moreover, comparison of brain organoids of human vs. non-human primate origin (macaque, chimpanzee, orang-utan) has led to the identification of human-specific features of neocortical development (Otani et al., 2016, Mora-Bermudez et al., 2016, Pollen et al., 2019, Kanton et al., 2019). Importantly, brain organoids can easily be genetically modified (Fischer et al., 2019), and human brain organoids have been shown to recapitulate gene expression patterns of fetal human neocortex (Camp et al., 2015). However, despite its promise, the brain organoid model system still has certain limitations, such that is does not fully recapitulate the cytoarchitecture, cell-type composition and late and postnatal stages of neocortex development (Heide et al., 2018). Moreover, cell-type specification in brain organoids seems to be impaired due to cellular stress (Bhaduri et al., 2020).

Hence, fetal human brain tissue ex vivo (Rakic, 2006, Florio et al., 2015, Johnson et al., 2015, Pollen et al., 2015, Kalebic et al., 2019, Namba et al., 2020) and non-human primate models (Smart et al., 2002, Rakic, 2006, Kelava et al., 2012, Garcia-Moreno et al., 2012, Betizeau et al., 2013) have been increasingly used to overcome the limitations of the rodent and ferret models and of brain organoids for studying the development of the neocortex with the aim to gain insight into the development and evolution of the human neocortex. However, the use of fetal human brain tissue ex vivo is limited to early stages of neocortical development, and genetic modification approaches can only be conducted – for obvious ethical reasons – with ex vivo fetal human brain tissue. It is for these reasons that genetically modifiable non-human primate models have recently emerged as system of choice to gain insight into human neocortex development and evolution (Sasaki et al., 2009, Niu et al., 2010, Niu et al., 2014, Shi et al., 2019, Heide et al., 2020). A major advantage of non-human primate models is that in terms of morphology, cell-type composition, gene expression and interaction partners, these models are much closer to human neocortex development than the rodent and ferret models. Moreover, genetically modifiable non-human primate models are likely to have huge potential in generating models of neurological and neurodevelopmental disorders.

ARHGAP11B — a human-specific gene that may drive human neocortex expansion and folding?

The ARHGAP11B gene evolved ~5 mya, that is, after the split of the lineage leading to modern humans and the lineage leading to chimpanzee and bonobo, by segmental duplication of the widespread gene ARHGAP11A (Sudmant et al., 2010). In other words, ARHGAP11B is only found in humans and hence is a human-specific gene. However, ARHGAP11B is not a simple copy of ARHGAP11A, as the ARHGAP11B protein corresponds to only the N-terminal one quarter of the ARHGAP11A protein and, importantly, possesses a unique, human-specific 47 amino acid sequence in its C-terminal domain that is key for its function (Florio et al., 2015, Namba et al., 2020). This unique C-terminal protein sequence arises from a single C-to-G nucleotide substitution in ARHGAP11B that generated a novel splice donor site, resulting in the loss of 55 nucleotides upon mRNA splicing. This loss in turn causes a shift in the reading frame, leading to ARHGAP11B’s unique C-terminal 47 amino acid sequence (Florio et al., 2016). Previous functional analyses by strong overexpression of this gene in embryonic mouse (Florio et al., 2015) and ferret (Kalebic et al., 2018) neocortex showed increased numbers of basal progenitor cells and of upper-layer neurons, the class of progenitors and type of cortical neurons, respectively, that have been implicated in neocortex expansion (Lui et al., 2011, Fame et al., 2011, Borrell and Reillo, 2012, Betizeau et al., 2013, Florio and Huttner, 2014, Dehay et al., 2015, Lodato and Arlotta, 2015). Moreover, in the case of mouse, ARHGAP11B overexpression could induce folding of the normally smooth neocortex (Florio et al., 2015). These findings suggested that ARHGAP11B is a candidate gene to have contributed to neocortex expansion and folding during human evolution. However, the key question was whether this gene, when expressed to physiological levels and in a primate model that is evolutionarily closer to human than mouse or ferret, would increase neocortex size and folding.

Which genetically modifiable non-human primate model to choose?

We therefore searched for a genetically modifiable primate model that is evolutionarily as close as (ethically) possible to human and that possesses all relevant stem cell populations at the correct relative abundance in the developing neocortex, to allow us to explore the potential role of ARHGAP11B in the expansion of the neocortex during development and human evolution. This confined our choice to two non-human primate models, the common marmoset (Callithrix jacchus) and the macaque (eitherMacaca mulatta or Macaca fascicularis). We chose to focus on the marmoset, as this New World monkey, while exhibiting many of the features of the large and folded human neocortex, has – in contrast to the macaque – a small and unfolded neocortex, making it thus an ideal model to study ARHGAP11B’s potential contribution to neocortical expansion and folding.

ARHGAP11B increases fetal primate neocortex size and folding

In Heide et al. 2020, we generated, in collaboration with the research groups of Erika Sasaki and Hideyuki Okano in Japan who have pioneered the transgenic marmoset technology (Sasaki et al., 2009), ARHGAP11B-transgenic marmoset fetuses (Figure A) that expressed ARHGAP11B in the developing neocortex under the control of its own, human promoter (Heide et al., 2020).

In the neocortex of these ARHGAP11B-transgenic marmoset fetuses, ARHGAP11B was expressed to physiological levels, that is, to similar levels as in fetal human neocortex, and its expression within the neocortex was confined to neural stem and progenitor cells (Heide et al., 2020). Furthermore, this ARHGAP11B expression increased the abundance of basal radial glia (Heide et al., 2020) – the basal progenitor cell type thought to play a key role in neocortex expansion and folding, notably in human neocortex development (Lui et al., 2011, Borrell and Reillo, 2012 Florio and Huttner, 2014). This was accompanied by an increase in upper-layer neurons (Heide et al., 2020) — the cortical neuron type thought to strongly contribute to our higher cognitive abilities (Fame et al., 2011). At the supracellular level, this ARHGAP11B expression resulted in increased neocortex size and induced folding of the normally unfolded fetal marmoset neocortex (Heide et al., 2020) (Figure B). In summary, our study strongly suggests that ARHGAP11B did contribute to neocortex expansion and folding in the course of human evolution.

Ethical considerations

Experiments involving non-human primates have been under constant public and scientific debate, and it is perfectly legitimate to scrutinize whether or not such experiments are really necessary and to ask whether other animal model systems are available that are appropriate to address the same scientific questions. Furthermore, experiments involving non-human primates should be performed according to the highest ethical standards.

In our case, we reasoned that in order to answer the question whether the human-specific gene ARHGAP11B contributed to neocortex expansion and folding during human evolution, it was necessary to express ARHGAP11B in a suitable non-human primate model, that is, the common marmoset. We limited these experiments and analyses to fetal stages, for two main reasons. First, should ARHGAP11Bexpression increase neocortex size and neuron numbers as we anticipated, the consequences for the postnatal and adult marmosets with regard to behaviour and nervous system performance might be unpredictable. In this context, one should realize that increases in neocortex size and neuron numbers are not necessarily beneficial but can be the underlying cause of certain human diseases (e.g., megalencephaly, polymicrogyria), and accordingly could lead to suffering of the animals (e.g., from seizures). To avoid generating ARHGAP11B-expressing postnatal and adult marmosets, all ARHGAP11B-expressing marmoset fetuses analyzed in our study were newly and individually generated (rather than being descendants of an ARHGAP11B-expressing marmoset line). Second, our previous data had indicated that ARHGAP11B expression increased basal progenitors and upper-layer neurons during the development of the neocortex. This suggested that in our case an analysis of fetal stages of ARHGAP11B-expressing marmosets would be appropriate and constructive, and would allow closely monitoring neocortex development and analyzing it at the relevant stages.

We hope that our study shows that genetically modified non-human primate fetuses can be superior models to understand human neocortex development and evolution. Furthermore, our work will hopefully encourage other researchers from the present and other fields of neurobiology (including disease modelling) to study genetically modified non-human primate models in the future, as (i) such experiments can be performed in an ethically justifiable way (see above), (ii) the results may answer questions that other, non-primate models cannot answer, and (iii) the results most likely can be directly translated to humans.

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Open postdoc position!

Interested in understanding how stretching affects tissue behaviour? Want to work in a brand new lab in a friendly and supportive environment?

Join the Tissue Architecture Lab at the Novo Nordisk Foundation Center for Stem Cell Biology, DanStem at Copenhagen University!

Here is the link to the open position https://employment.ku.dk/faculty/?show=152331 and the link to the lab website https://danstem.ku.dk/research1/aragona/group-research/

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By Fei Zhang and Vivian F. Irish

Flowering plants, from giant sequoias to miniscule duckweed, all depend on the action of small populations of cells, called meristems, to grow.  Meristems contain stem cells that continue to proliferate to give rise to roots, shoots, leaves, and branches. However, there are situations in which meristematic cells cease their proliferative activity and terminally differentiate; this occurs in flowers, and floral specific gene networks have been identified that terminate stem cell activity as flower development ensues. A far less well studied example of meristem termination is the formation of thorns. A number of plant species equip themselves with thorns to deter herbivores yet little is known of how these weapons are made.

Over ten years ago, our group set out to understand how meristematic activity is arrested during thorn development. Citrus was selected as a model for thorn development for two reasons: agronomic importance and feasibility. Citrus is one of the most economically valuable fruit crops in the world, and thornlessness is a breeding target as thorns affect fruit harvesting efficiency and can physically damage fruits. In addition, research in citrus is practical: the genome sequences of several citrus species are available, there are naturally occurring citrus variants that lack thorns, and citrus is amenable to genetic transformation. As tractable mutants are key for functional genetics studies, we established a fast and efficient citrus genome editing system by using the YAO promoter to drive Cas9 expression and employed heat stress treatments to further increase CRISPR-mediated gene editing efficiency. This system has proven to be very effective and we can now inactivate up to six genes simultaneously in primary citrus transformants in just a few months.

In our recent paper, Zhang et al 2020, we first characterized thorn growth and defined stages from primordium initiation to terminal differentiation. At early stages, the thorn primordia appear dome-shaped, like that of typical shoot meristems. By stage 7, the thorn tip narrows and at stage 8, thorns elongate and become pointed. Furthermore, the expression of two meristem-expressed genes, SHOOT MERISTEMLESS (STM) and WUSCHEL (WUS) are downregulated at stage 8, with STM expression becoming confined to vascular tissues and WUS expression becoming undetectable. Cell division completely ceases by stage 13, and the thorn lignifies to produce the sharp hard stiletto-like tip.

The question that naturally arises is what terminates thorn meristem gene expression at stage 8. Using a thornless Mexican lime natural variant in comparison to normal Mexican limes, we performed transcriptome analyses of young shoots. We focused on differentially expressed transcription factors that are expressed preferentially in young thorns. One candidate gene, THORN IDENTITY1, encodes a TCP transcription factor, and its homologues control bud dormancy in other plant species and so was an excellent candidate for further analyses. Interestingly, TI1 expression starts at stage 8, and a CRISPR-induced mutation of TI1 leads to the transformation of some thorns into branches. TI1 has a paralogue in citrus, TI2, whose expression in thorns starts from stage 7, and a ti2 mutation also shows the thorn transformed into branch phenotype. Mutation of TI1 and TI2 together transforms nearly every thorn into a branch, resulting in a very bushy phenotype (Figure 1).

WUS expression is upregulated in ti1, ti2 and ti1ti2 mutants, suggesting that the TI genes may function through repressing WUS transcription. Supporting this, both TI1 and TI2 repress WUS promoter activity in transient expression assays, and TI1 directly binds to the WUS promoter as demonstrated by both chromatin immunoprecipitation and gel shift assays.  Interestingly, the citrus WUS promoter has a TCP consensus binding site that is not present in the model plant Arabidopsis thaliana, and we showed that mutation of this cis-element can abolish TI1-WUS promoter regulation. Finally, disruption of the TI1–WUS pathway by either ectopic expression of WUS or via a WUS promoter mutation affects thorn development, indicating that this pathway is critical for thorn growth.

In the classic textbook “Patterns in Plant Development”, by Taylor Steeves and Ian Sussex, thorns are viewed as “one of the most striking departures from typical shoot morphology”. Our work serves as a first step for understanding how such evolutionary novelties arise. With the identification of citrus thorn identity TI genes and a previously undescribed TI–WUS pathway for stem cell regulation, we now have a handle to explore the upstream and downstream regulators involved in weaponizing plants. It is also worth mentioning that thorns have evolved multiple times, and can exhibit very striking departures from shoots, for instance as in honey locust thorns (Figure 2). It still remains to be seen if different plant species redeploy the TI-WUS pathway for thorn development, or if different species armor themselves in unique ways.

Fei Zhang, Pascale Rossignol, Tengbo Huang, Yewei Wang, Alan May, Christopher Dupont, Vladimir Orbovic, Vivian F. Irish. 2020. ‘Reprogramming of Stem Cell Activity to Convert Thorns into Branches’. Current Biology 

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