Our latest monthly trawl for developmental biology (and other cool) preprints. Let us know if we missed anything.

This month in preprint news – here at The Company of Biologists, set just outside Cambridge in the UK, we’re hiring a new ‘Preprints Community Manager’. You can find out more here. It’s a great opportunity to get in to science communication and publishing, and of course preprints!

And this month in preprints, we found platypuses and pigeons, xenotransplants and reoriented axes,  CRISPR tools and liquid droplets. The preprints were hosted on bioRxiv, PeerJ, 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

Evo-devo & evo

Cell biology

Modelling

Tools & resources

| Imaging etc.

| Genome tools

Research practice

Why not…

Developmental biology

| Patterning & signalling

Reorientation of the primary body axis by ectopic embryonic cWnt signaling. Mark Q Martindale, Naveen Wijesena

High fidelity lineage tracing in mouse pre-implantation embryos using primed conversion of photoconvertible proteins. Maaike Welling,  Manuel A. Mohr, Aaron Ponti, Lluc R. Sabater, Andrea Boni, Prisca Liberali, Pawel Pelczar, Periklis Pantazis

Caudal counter-represses Hunchback to regulate even-skipped stripe 2 expression in Drosophila embryos. Ben J Vincent, Max V Staller, Francheska Lopez-Rivera, Meghan DJ Bragdon, Zeba Wunderlich, Javier Estrada, Angela H DePace

A damped oscillator imposes temporal order on posterior gap gene expression in Drosophila. Berta Verd, Erik Clark, Karl R. Wotton, Hilde Janssens, Eva Jimenez-Guri, Anton Crombach, Johannes Jaeger

From pioneer to repressor: Bimodal foxd3 activity dynamically remodels neural crest regulatory landscape in vivo. Daria Gavriouchkina, Ruth M Williams, Martyna Lukoseviciute, Tatiana Hochgreb-Hagele, Upeka Senanayake, Vanessa Chong-Morrison, Supat Thongjuea, Emmanouela Repapi, Adam Mead, Tatjana Sauka-Spengler

Embryonic circular RNAs at tandem duplicated genes in zebrafish present new paradigm in gene expression. Vanessa Chong-Morrison, Tatjana Sauka-Spengler

Diversification of heart progenitor cells by EGF signaling and differential modulation of ETS protein activity. Benjamin Schwarz, Dominik Hollfelder, Katharina Scharf, Leonie Hartmann, Ingolf Reim

Single cell RNA-seq and ATAC-seq indicate critical roles of Isl1 and Nkx2-5 for cardiac progenitor cell transition states and lineage settlement. Guangshuai Jia, Jens Preussner, Stefan Guenther, Xuejun Yuan, Michail Yekelchyk, Carsten Kuenne, Mario Looso, Yonggang Zhou, Thomas Braun

Early Subset Of Cerebellar Nuclei Neurons Derived From Mesencephalon In Mice. Maryam Rahimi-Balaei, Xiaodan Jiao, Fiona Parkinson, Behzad Yeganeh, Hassan Marzban

Elevated and sustained reactive oxygen species levels facilitate mesoderm formation during early Xenopus development. Yue Han, Yaoyao Chen, Nick R Love, Shoko Ishibashi, Enrique Amaya

Ca2+-induced mitochondrial ROS regulate the early embryonic cell cycle. Yue Han, Shoko Ishibashi, Javier Iglesias-Gonzalez, Yaoyao Chen, Nick R Love, Enrique Amaya

Proteomics of phosphorylation and protein dynamics during fertilization and meiotic exit in the Xenopus egg. Marc Stuart Presler, Elizabeth Van Itallie, Allon M. Klein, Ryan Kunz, Peg Coughlin, Leonid Peshkin, Steven Gygi, Martin Wühr, Marc Kirschner

Maternal proteins that are phospho-regulated upon egg activation include crucial factors for oogenesis, egg activation and embryogenesis in Drosophila melanogaster. Zijing Zhang, Amber R. Krauchunas, Stephanie Huang, Mariana F. Wolfner

Endodermal differentiation is reconstructed by coordination of two parallel signaling systems derived from the stele in roots. Pengxue Li, Qiaozhi Yu, Chunmiao Xu, Xu Gu, Shilian Qi, Hong Wang, Fenglin Zhong, Shuang Wu

Minimum requirements for reprogramming and maintaining cell fate in the Arabidopsis root. Colleen Drapek, Erin E. Sparks, Peter Marhavy, Tonni G. Andersen, Jessica H. Hennacy, Niko Geldner, Philip N. Benfey

LRX Proteins play a crucial role in pollen grain and pollen tube cell wall development. Tohnyui Ndinyanka Fabrice, Hannes Vogler, Christian Draeger, Gautam Munglani, Shibu Gupta, Aline Galatea Herger, Paul Knox, Ueli Grossniklaus, Christoph Ringli

Hominin-specific NOTCH2 paralogs expand human cortical neurogenesis through regulation of Delta/Notch interactions. Ikuo K Suzuki, David Gacquer, Roxane Van Heurck, Devesh Kumar, Marta Wojno, Angeline Bilheu, Adele Herpoel, Julian Cheron, Franck Polleux, Vincent Detours, Pierre Vanderhaeghen

Human-specific NOTCH-like genes in a region linked to neurodevelopmental disorders affect cortical neurogenesis. Ian T Fiddes, Gerrald A Lodewijk, Meghan M Mooring, Colleen M Bosworth, Adam D Ewing, Gary L Mantalas, Adam M Novak, Anouk van den Bout, Alex Bishara, Jimi L Rosenkrantz, Ryan Lorig-Roach, Andrew R Field, Maximillian Haeussler, Lotte Russo, Aparna Bhaduri, Tomasz J Nowakowski, Alex A Pollen, Max L Dougherth, Xander Nuttle, Marie-Claude Addor, Simon Zwolinski, Sol Katzman, Arnold Kreigstein, Evan E Eichler, Sofie R Salama, Frank MJ Jacobs, David Haussler

Skeletal muscle fibro-adipogenic progenitors of dystrophic mice are insensitive to NOTCH-dependent regulation of adipogenesis. Milica Marinkovic, Francesca Sacco, Filomena Spada, Lucia Lisa Petrilli, Claudia Fuoco, Elisa Micarelli, Theodora Pavlidou, Luisa Castagnoli, Matthias Mann, Cesare Gargioli, Gianni Cesareni

NOTCH-mediated non-cell autonomous regulation of chromatin structure during senescence. Aled J Parry, Matthew Hoare, Dóra Bihary, Robert Hänsel-Hertsch, Stephen Smith, Kosuke Tomimatsu, Shankar Balasubramanian, Hiroshi Kimura, Shamith Samarajiwa, Masashi Narita

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

An atlas of Caenorhabditis elegans chemoreceptor expression. Berta Vidal, Ulkar Aghayeva, Haosheng Sun, Chen Wang, Lori Glenwinkel, Emily Bayer, Oliver Hobert

Bidirectional Cycling Dynamics of Living Neuronal Networks in Vitro. Arseniy Gladkov, Oleg Grinchuk, Yana Pigareva, Irina Mukhina, Victor Kazantsev, Alexey Pimashkin

Loss of Wt1 in the murine spinal cord alters interneuron composition and locomotion. Danny Schnerwitzki, Sharn Perry, Anna Ivanova, Fabio Viegas Caixeta, Paul Cramer, Sven Guenther, Kathrin Weber, Atieh Tafreshiha, Lore Becker, Ingrid L. Vargas Panesso, Thomas Klopstock, Martin Hrabe de Angelis, Manuela Schmidt, Klas Kullander, Christoph Englert

Smad9 is a key player of follicular selection in goose via keeping the balance of LHR transcription. Daolun Yu, Fanghui Chen, Li Zhang, Hejian Wang, Jie Chen, Zongmeng Zhang, Jie Li, Chaofeng Xing, Honglin Li, Jun Li, Yafei Cai

Widespread dynamic and pleiotropic expression of the melanocortin-1-receptor (MC1R) system is conserved across chick, mouse and human embryonic development. Anna Thomas, Pauline Heux, Chloe Santos, Wisenave Arulvasan, Nita Solanky, Magalie E. Carey, Dianne Gerrelli, Veronica A. Kinsler, Heather C. Etchevers

| Morphogenesis & mechanics

Size-reduced embryos reveal a gradient scaling based mechanism for zebrafish somite formation. Kana Ishimatsu, Tom W Hiscock, Zach M Collins, Dini Wahyu Kartika Sari, Kenny Lischer, David L. Richmond, Yasumasa Bessho, Takaaki Matsui, Sean G Megason

Spatio-temporal elasticity patterns in extracellular matrix during Hydra morphogenesis. Mariam Veschgini, Hendrik O Petersen, Wasim Abuillan, Fernanda F Rossetti, Suat Özbek, Manfred Burghammer, Thomas W Holstein, Motomu Tanaka

Selective Filopodia Adhesion Ensures Robust Cell Matching in the Drosophila Heart. ShaoBo Zhang, Christopher Amourda, Timothy Saunders

Junction-based lamellipodia drive endothelial cell rearrangements in vivo via a VE-cadherin/F-actin based oscillatory ratchet mechanism. Ilkka Paatero, Loic Sauteur, MInkyoung Lee, Anne Karine Lagendijk, Daniel Heutschi, Dimitri Bieli, Benjamin M. Hogan, Markus Affolter, Heinz-Georg Belting

Actomyosin contractility modulates Wnt signaling through adherens junction stability. Eric T. Hall, Elizabeth A. Hoesing, Endre D. Sinkovics, Esther M. Verheyen

PI(4,5)P2 forms dynamic cortical structures and directs actin distribution and cell polarity in C. elegans embryos. Melina J. Scholze, Kevin S. Barbieux, Alessandro De Simone, Mathilde Boumasmoud, Camille C. N. Suess, Ruijia Wang, Pierre Gonczy

Atf3 links loss of epithelial polarity to defects in cell differentiation and cytoarchitecture. Colin D. Donohoe, Andreia Correia, Gabor Csordas, Marek Jindra, Corinna Klein, Bianca Habermann, Mirka Uhlirova

Cerebellar granule cell precursors can extend processes, undergo short migratory movements and express postmitotic markers before mitosis in the chick EGL. Michalina Hanzel, Richard JT Wingate

Axons from the trigeminal ganglia are the earliest afferent projections to the mouse cerebellum. Hassan Marzban, Maryam Rahimi Balaei, Richard Hawkes

Formin3 regulates dendritic architecture via microtubule stabilization and is required for somatosensory nociceptive behavior. Ravi Das, Jamin M Letcher, Jenna M Harris, Istvan Foldi, Sumit Nanda, Hansley M Bobo, József Mihály, Giorgio A Ascoli, Daniel N Cox

Effects of mutating α-tubulin lysine 40 on sensory dendrite development. Brian Jenkins, Harriet A. J. Saunders, Helena L. Record, Dena M. Johnson-Schlitz, Jill Wildonger

Anisotropic Cellular Mechanoresponse for Radial Size Maintenance of Developing Epithelial Tubes. Tsuyoshi Hirashima, Taiji Adachi

Live imaging of heart tube development in mouse reveals alternating phases of cardiac differentiation and morphogenesis. Kenzo Ivanovitch, Susana Temino, Miguel Torres

| Genes & genomes

Transgenerational Epigenetic Inheritance Factors Localize to Spatially and Temporally Ordered Liquid Droplet Assemblages. Gang Wan, Brandon Fields, George Spracklin, Carolyn Phillips, Scott Kennedy

Olig2 and Hes regulatory dynamics during motor neuron differentiation revealed by single cell transcriptomics. Andreas Sagner, Zachary Gaber, Julien Delile, Jennifer H. Kong, David L. Rousso, Caroline A. Pearson, Steven E. Weicksel, Manuela Melchionda, Neda Mousavy Gharavy, James Briscoe, Bennett Novitch

Integrated analysis of single-cell embryo data yields a unified transcriptome signature for the human preimplantation epiblast. Giuliano G Stirparo, Thorsten Boroviak, Ge Guo, Jennifer Nichols, Austin Smith, Paul Bertone

Allele-specific control of replication timing and genome organization during development. Juan Carlos Rivera-Mulia, Andrew Dimond, Daniel Vera, Claudia Trevilla-Garcia, Takayo Sasaki, Jared Zimmerman, Catherine Dupont, Joost Gribnau, Peter Fraser, David M Gilbert

The conserved LEM-3/Ankle1 nuclease is involved in the combinatorial regulation of meiotic recombination repair and chromosome segregation in Caenorhabditis elegans. YE HONG, Maria Velkova, Nicola Silva, Marlene Jagut, Viktor Scheidt, Karim Labib, Verena Jantsch, Anton Gartner

Re-arrangements in the cytoplasmic distribution of small RNAs following the maternal-to-zygotic transition in Drosophila embryos. Mehmet Ilyas Cosacak, Hatice Yigit, Bunyamin Akgul

Smg5 is required for multiple nonsense-mediated mRNA decay pathways in Drosophila. Jonathan O. Nelson, Dominique Foerster, Kimberly Frizzell, Stefan Luschnig, Mark M. Metzstein

Quantitative RNAseq Meta Analysis Of Alternative Exon Usage In C. elegans. Nicolas J. Tourasse, Jonathan R. M. Millet, Denis Dupuy

Dynamic reorganization of nuclear architecture during human cardiogenesis. Paul A Fields, Vijay Ramani, Giancarlo Bonora, Galip Gurkan Yardimci, Alessandro Bertero, Hans Reinecke, Lil Pabon, William S Noble, Jay Shendure, Charles Murry

Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues. Erin E. Terry, Xiping Zhang, Christy Hoffmann, Laura D. Hughes, Scott A. Lewis, Jiajia Li, Lance Riley, Nicholas F. Lahens, Ming Gong, Francisco Andrade, Karyn A. Esser, Michael E. Hughes

Deciphering cis-regulatory logic with 100 million synthetic promoters. Carl de Boer, Ronen Sadeh, Nir Friedman, Aviv Regev

Spatially varying cis-regulatory divergence in Drosophila embryos elucidates cis-regulatory logic. Peter A. Combs, Hunter B. Fraser

Determinants of Transcription Initiation Directionality in Metazoans. Mahmoud M Ibrahim, Aslihan Karabacak, Alexander Glahs, Ena Kolundzic, Antje Hirsekorn, Alexa Carda, Baris Tursun, Robert P Zinzen, Scott A Lacadie, Uwe Ohler

Transcription start site analysis reveals widespread divergent transcription in D. melanogaster and core promoter encoded enhancer activities. Sarah Rennie, Maria Dalby, Marta Lloret-Llinares, Stylianos Bakoulis, Christian Dalager Vaagenso, Torben Heick Jensen, Robin Andersson

Higher-order inter-chromosomal hubs shape 3-dimensional genome organization in the nucleus. Sofia A Quinodoz, Noah Ollikainen, Barbara Tabak, Ali Palla, Jan Marten Schmidt, Elizabeth Detmar, Mason Lai, Alexander Shishkin, Prashant Bhat, Vickie Trinh, Erik Aznauryan, Pamela Russell, Christine Cheng, Marko Jovanovic, Amy Chow, Patrick McDonel, Manuel Garber, Mitchell Guttman

CHRAC/ACF Contribute to the Repressive Ground State of Chromatin. Alessandro Scacchetti, Laura Brueckner, Dhawal Jain, Tamas Schauer, Xu Zhang, Frank Schnorrer, Bas van Steensel, Tobias Straub, Peter B. Becker

Strong binding activity of few transcription factors is a major determinant of open chromatin. Bei Wei, Arttu Jolma, Biswajyoti Sahu, Lukas M. Orre, Fan Zhong, Fangjie Zhu, Teemu Kivioja, Inderpreet Kaur Sur, Janne Lehtio, Minna Taipale, Jussi Taipale

Chromatin-release of the long ncRNA A-ROD is required for transcriptional activation of its target gene DKK1. Evgenia Ntini, Julia Liz, Jose M Muino, Annalisa Marsico, Ulf Andersson Oerom

LEM-3 is a midbody-tethered DNA nuclease that resolves chromatin bridges during cytokinesis. YE HONG, Remi Sonneville, Bin Wang, Viktor Scheidt, Bettina Meier, Alexander Woglar, Sarah Demetriou, Karim Labib, Verena Jantsch, Anton Gartner

Profiling of accessible chromatin regions across multiple plant species and cell types reveals common gene regulatory principles and new control modules. Kelsey A. Maher, Marko Bajic, Kaisa Kajala, Mauricio Reynoso, Germain Pauluzzi, Donnelly A. West, Kristina Zumstein, Margaret Woodhouse, Kerry Bubb, Mike Dorrity, Christine Queitsch, Julia Bailey-Serres, Neelima Sinha, Siobhan M. Brady, Roger B. Deal

Chromatin accessibility changes between Arabidopsis stem cells and mesophyll cells illuminate cell type-specific transcription factor networks. Paja Sijacic, Marko Bajic, Elizabeth C. McKinney, Richard B. Meagher, Roger B. Deal

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

Distinct stimulatory mechanisms regulate the catalytic activity of Polycomb Repressive Complex 2 (PRC2). Chul-Hwan Lee, Marlene Holder, Daniel Grau, Ricardo Saldana-Meyer, Rais Ahmad Ganai, Jenny Zhang, Miao Wang, Marc-Werner Dobenecker, Danny Reinberg, Karim-Jean Armache

Functional redundancy of variant and canonical histone H3 lysine 9 modification in Drosophila. Taylor J. R. Penke, Daniel J. McKay, Brian D. Strahl, A. Gregory Matera, Robert J. Duronio

The function of the prereplicative complex and SCF complex components during Drosophila wing development. Hidetsugu Kohzaki

PWO1 interacts with PcG proteins and histones to regulate Arabidopsis flowering and development. Mareike L Hohenstatt, Pawel Mikulski, Olga Komarynets, Constanze Klose, Ina Kycia, Albert Jeltsch, Sara Farrona, Daniel Schubert

PWWP INTERACTOR OF POLYCOMBS (PWO1) links PcG-mediated gene repression to the nuclear lamina in Arabidopsis. Pawel Mikulski, Mareike L Hohenstatt, Sara Farrona, Cezary Smaczniak, Kerstin Kaufmann, Gerco Angenent, Daniel Schubert

The HoxD Cluster is a Dynamic and Resilient TAD Boundary Controling the Segregation of Antagonistic Regulatory Landscapes. Eddie Rodriguez-Carballo, Lucille Lopez-Delisle, Ye Zhan, Pierre Fabre, Leonardo Beccari, Imane El-Idrissi, Thi Hahn Nguyen Huynh, Hakan Ozadam, Job Dekker, Denis Duboule

Cohesin facilitates zygotic genome activation in zebrafish. Michael Meier, Jenny Grant, Amy Dowdle, Amarni Thomas, Jennifer E. Gerton, Philippe Collas, Justin M. O’Sullivan, Julia A. Horsfield

CTCF mediated genome architecture regulates the dosage of mitotically stable mono-allelic expression of autosomal genes. Keerthivasan Raanin Chandradoss, Kuljeet Singh Sandhu

Interdependent and separable functions of C. elegans MRN-C complex members couple formation and repair of meiotic DSBs. Chloe Girard, Baptiste Roelens, Karl A. Zawadzki, Anne M. Villeneuve

LINE-2 transposable elements shape post-transcriptional gene regulation in the human brain. Rebecca Petri, Per Ludvik Brattås, Marie E. Jönsson, Karolina Pircs, Johan Bengzon, Johan Jakobsson

No kissing in the nucleus: Unbiased analysis reveals no evidence of trans chromosomal regulation of mammalian immune development. Timothy M Johanson, Hannah D Coughlan, Aaron TL Lun, Naiara G Bediaga, Gaetano Naselli, Alexandra L Garnham, Leonard C Harrison, Gordon K Smyth, Rhys S Allan

The Transcriptional Logic of Mammalian Neuronal Diversity. Ken Sugino, Erin Clark, Anton Schulmann, Yasuyuki Shima, Lihua Wang, David L. Hunt, Bryan M. Hooks, Dimitri Trankner, Jayaram Chandrashekar, Serge Picard, Andrew Lemire, Nelson Spruston, Adam Hantman, Sacha B. Nelson

| Stem cells, regeneration & disease modelling

Signaling-dependent control of apical membrane size and self-renewal in rosette-stage human neuroepithelial stem cells. Jan-Philip Medelnik, Kathleen Roensch, Satoshi Okawa, Antonio del Sol, Osvaldo Chara, Levan Mchedlishvili, Elly Tanaka

Fractone bulbs derive from ependymal cells and their laminin composition influence the stem cell niche in the subventricular zone. Marcos Assis Nascimento, Lydia Sorokin, Tatiana Coelho-Sampaio

Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPS cells. Kai Fu, Constantinos Chronis, Abdenour Soufi, Giancarlo Bonora, Miguel Edwards, Steve Smale, Kenneth Zaret, Kathrin Plath, Matteo Pellegrini

Differentiation of primate primordial germ cell-like cells following transplantation into the adult gonadal niche. Enrique Sosa, Di Chen, Ernesto J Rojas, Jon Hennebold, Karen Peters, Zhuang Wu, Truong N Lam, Jennifer Mitchell, Ramesh Tailor, Marvin Meistrich, Kyle Orwig, Gunapala Shetty, Amander T Clark

Temporal epigenomic profiling identifies AHR as dynamic super-enhancer controlled regulator of mesenchymal multipotency. Deborah Gerard, Florian Schmidt, Aurelien Ginolhac, Martine Schmitz, Rashi Halder, Peter Ebert, Marcel H. Schulz, Thomas Sauter, Lasse Sinkkonen

Comparison of multiple transcriptomes exposes unified and divergent features of quiescent and activated skeletal muscle stem cells. Natalia Pietrosemoli, Sebastien Mella, Siham Yennek, Meryem Baghdadi, Hiroshi Sakai, Ramkumar Sambasivan, Francesca Pala, DANIELA DI GIROLAMO, Shahragim Tajbakhsh

Single-cell quantitative analysis of skeletal muscle cell population dynamics during regeneration and ageing. Lucia Lisa Petrilli, Filomena Spada, Claudia Fuoco, Elisa Micarelli, Alessio Reggio, Marco Rosina, Cesare Gargioli, Luisa Castagnoli, Gianni Cesareni

Heterogeneous Responses of Hematopoietic Stem Cells to Inflammatory Stimuli are Altered with Age. Mati Mann, Arnav Mehta, Carl de Boer, Monika S. Kowalczyk, Kevin Lee, Noga Rogel, Abigail R. Knecht, Daneyal Farouq, Aviv Regev, David Baltimore

T helper cells modulate intestinal stem cell renewal and differentiation. Moshe Biton, Adam Haber, Semir Beyaz, Noga Rogel, Christopher Smillie, Karthik Shekhar, Alexandra Schnell, Zuojia Chen, Chuan Wu, Jose Ordovas-Montanes, David Alvarez, Rebecca H. Herbst, Itay Tirosh, Grace Burgin, Danielle Dionne, Michael E. Xifaras, Mei Zhang, Alex K. Shalek, Ulrich H. von Andrian, Daniel B. Graham, Orit Rozenblatt-Rosen, Hai Ning Shi, Vijay Kuchroo, Omer Yilmaz, Aviv Regev, Ramnik J. Xavier

The CD11a and EPCR marker combination simplifies and improves the purification of mouse hematopoietic stem cells. Alborz Karimzadeh, Vanessa Scarfone, Connie Chao, Karin Grathwohl, John W. Fathman, David Fruman, Thomas Serwold, Matthew Inla

Instructive starPEG-Heparin biohybrid 3D cultures for modeling human neural stem cell plasticity, neurogenesis, and neurodegeneration. Christos Papadimitriou, Mehmet I Cosacak, Violeta Mashkaryan, Hilal Celikkaya, Laura Bray, Prabesh Bhattarai, Heike Hollak, Xin Chen, Shuijin He, Christopher L Antos, Alvin Thomas, Jens Friedrichs, Andreas Dahl, Yixin Zhang, Uwe Freudenberg, Carsten Werner, Caghan Kizil

Intestinal crypts recover rapidly from focal damage with coordinated motion of stem cells that is impaired by aging. Jiahn Choi, Nikolai Rakhilin, Poornima Gadamsetty, Daniel J. Joe, Tahmineh Tabrizian, Steven M. Lipkin, Derek Huffman, Xiling Shen, Nozomi Nishimura

Generation of Mouse-Zebrafish Hematopoietic Tissue Chimeric Embryos for Hematopoiesis and Host-Pathogen Interaction Studies. Margarita M. Parada-Kusz, Anne Clatworthy, Elliott J. Hagedorn, Cristina Penaranda, Anil V. Nair, Jonathan E. Henninger, Christoph Ernst, Brian Li, Raquel Riquelme, Humberto Jijon, Eduardo J. Villablanca, Leonard I. Zon, Deborah Hung, Miguel Allende

Continuous high-resolution in vivo imaging reveals tumor-specific dissemination in an embryonic zebrafish xenograft model. Nandini Asokan, Stephan Daetwyler, Stefanie Nadine Bernas, Christopher Schmied, Steffen Volger, Katrin Lambert, Manja Wobus, Martin Wermke, Gerd Kempermann, Jan Huisken, Michael Brand, Martin Bornhaeuser

Mutations in C11ORF70 cause primary ciliary dyskinesia with randomization of left/right body asymmetry due to outer and inner dynein arm defects. Inga M Höben, Rim Hjeij, Heike Olbrich, Gerard W Dougherty, Tabea Menchen, Isabella Aprea, Diana Frank, Petra Pennekamp, Bernd Dworniczak, Julia Wallmeier, Johanna Raidt, Kim G Nielsen, Maria C Philipsen, Francesca Santamaria, Laura Venditto, Israel Amirav, Freerk Prenzel, Kaman Wu, Miriam Schmidts, Niki T Loges, Heymut Omran

A phase separated organelle at the root of motile ciliopathy. Ryan Huizar, Chanjae Lee, Alexander Boulgakov, Amjad Horani, Fan Tu, Kevin Drew, Edward Marcotte, Steven Brody, John Wallingford

Phenotyping ciliary dynamics and coordination in response to CFTR-modulators in Cystic Fibrosis respiratory epithelial cells. Maurizio Chioccioli, Luigi Feriani, Jurij Kotar, Preston E. Bratcher,  Pietro Cicuta

Gene expression in cord blood links genetic risk for neurodevelopmental disorders with maternal psychological distress and adverse childhood outcomes. Michael S. Breen, Aliza P. Wingo, Nastassja Koen, Kirsten A. Donald, Heather J. Zar, Kerry J. Ressler, Joseph D. Buxbaum, Dan J. Stein

Developmental And Genetic Regulation Of The Human Cortex Transcriptome In Schizophrenia. Andrew E Jaffe, Richard E Straub, Joo Heon Shin, Ran Tao, Yuan Gao, Leonardo Collado Torres, Tony Kam-Thong, Hualin S Xi, Jie Quan, Qiang Chen, Carlo Colantuoni, William S Ulrich, Brady J Maher, Amy Deep-Soboslay, The BrainSeq Consortium, Alan Cross, Nicholas J Brandon, Jeffrey T Leek, Thomas M Hyde, Joel E Kleinman, Daniel R Weinberger

Gene expression imputation across multiple brain regions reveals schizophrenia risk throughout development. Laura M Huckins, Amanda Dobbyn, Douglas Ruderfer, Gabriel Hoffman, Weiqing Wang, Antonio F Pardinas, Veera M Rajagopal, Thomas D Als, Hoang Tan Hoang, Kiran Girdhar, James Boocock, Panagiotis Roussos, Menachem Fromer, Robin Kramer, Enrico Domenici, Eric Gamazon, Shaun Purcell, CommonMind Consortium, Schizophrenia Working Group of the Psychiatric Gen, iPSYCH-GEMS Schizophrenia Working Group, Ditte Demontis, Anders Borglum, James Walters, Michael O’Donovan, Patrick F Sullivan, Micahel Owen, Bernie Devlin, Solveig K Sieberts, Nancy Cox, Hae Kyung Im, Pamela Sklar, Eli Ayumi Stahl

Germ line aging and regional epigenetic instability: age prediction using human sperm DNA methylation signatures. Timothy G Jenkins, Kenneth I Aston, Douglas T Carrell

Aging and neurodegeneration are associated with increased mutations in single human neurons. Michael A Lodato, Rachel E Rodin, Craig L Bohrson, Michael E Coulter, Alison R Barton, Minseok Kwon, Maxwell A Sherman, Carl M Vitzhum, Lovelace J Luquette, Chandri Yandava, Pengwei Yang, Thomas W Chittenden, Nicole E Hatem, Steven C Ryu, Mollie B Woodworth, Peter J Park, Christopher A Walsh

Epigenetic influences on aging: a longitudinal genome-wide methylation study in old Swedish twins. Yunzhang Wang, Robert Karlsson, Erik Lampa, Qian Zhang, Åsa K. Hedman, Malin Almgren, Catarina Almqvist, Allan F. McRae, Riccardo Marioni, Erik Ingelsson, Peter M. Visscher, Ian J. Deary, Lars Lind, Tiffany Morris, Stephan Beck, Nancy L. Pedersen, Sara Hägg

Identification of key pathways and metabolic fingerprints of longevity in C. elegans. Arwen Gao, Reuben Smith, Michel Van Weeghel, Rashmi Kamble, Riekelt Houtkooper

An essential post-developmental role for Lis1 in mice. Timothy J Hines, Xu Gao, Subhshri Sahu, Meghann M Lange, Jill R Turner, Jeffery L Twiss, Deanna S Smith

A urine-dependent human urothelial organoid offers a promising alternative to rodent models of infection. Harry Horsley, Dhanuson Dharmasena, James Malone-Lee, Jennifer L. Rohn

Germline loss of MBD4 predisposes to leukaemia due to a mutagenic cascade driven by 5mC. Mathijs A. Sanders, Edward Chew, Christoffer Flensburg, Annelieke Zeilemaker, Sarah E. Miller, Adil al Hinai, Ashish Bajel, Bram Luiken, Melissa Rijken, Tamara Mclennan, Remco M. Hoogenboezem, François G. Kavelaars, Marnie E. Blewitt, Eric M. Bindels, Warren S. Alexander, Bob Löwenberg, Andrew W. Roberts, Peter J. M. Valk, Ian Majewski

An Essential Role for Argonaute 2 in EGFR-KRAS Signaling in Pancreatic Cancer Development. Sunita Shankar, Jean Tien, Ronald F Siebenaler, Vijaya L Dommeti, Sylvia Zelenka-Wang, Kristin M Juckette, Alice Xu, Malay Mody, Andrew Goodrum, Grace Tsaloff, Ingrid J Apel, Lisha Wang, Javed Siddiqui, Jiaqi Shi, Chandan Kumar-Sinha, Arul M Chinnaiyan

Neutrophil adhesion in brain capillaries contributes to cortical blood flow decreases and impaired memory function in a mouse model of Alzheimer’s disease. Jean C. Cruz Hernandez, Oliver Bracko, Calvin J. Kersbergen, Victorine Muse, Mohammad Haft-Javaherian, Maxime Berg, Laibaik Park, Lindsay K. Vinarcsik, Iryna Ivasyk, Yiming Kang, Marta Cortes-Canteli, Myriam Peyrounette, Vincent Doyeux, Amy Smith, Joan Zhou, Gabriel Otte, Jeffrey D. Beverly, Elizabeth Davenport, Yohan Davit, Sidney Strickland, Costantino Iadecola, Sylvie Lorthois, Nozomi Nishimura, Chris B. Schaffer

PPARD regulation in gastric progenitor cells drives gastric tumorigenesis in mice. Xiangsheng Zuo, Yasunori Deguchi, Weiguo Xu, Daoyan Wei, Rui Tian, Weidong Chen, Micheline J. Moussalli, Yi Liu, Fei Mao, Min Xu, Yaying Yang, Shen Gao, Jonathan C. Jaoude, Fuyao Liu, Mihai Gagea, Russell Broaddus, Keping Xie, Imad Shureiqi

L-tyrosine supplementation is not therapeutic for skeletal muscle dysfunction in zebrafish and mouse models of dominant skeletal muscle α-actin nemaline myopathy. Adriana M. Messineo, Charlotte Gineste, Tamar E. Sztal, Elyshia L McNamara, Christophe Vilmen, Augustin C. Ogier, Dorothee Hahne, David Bendahan, Nigel G. Laing, Robert J. Bryson-Richardson, Julien Gondin, Kristen J. Nowak

Determining the genetic basis of anthracycline-cardiotoxicity by molecular response QTL mapping in induced cardiomyocytes. David A. Knowles, Courtney K. Burrows, John D. Blischak, Kristen M. Patterson, Carole Ober, Jonathan K. Pritchard, Yoav Gilad

Endothelial Cell-Specific MCPIP Deletion Causes Endothelial Dysfunction and Impairs Post-ischemic Angiogenesis in Vivo. Jianli Niu, Nidhi Kapoor, Jian Liang, Zhuqing Jin, Edilu Becerra, Pappachan E. Kolattukudy

PKD2 is an essential ion channel subunit in the primary cilium of the renal collecting duct epithelium. Xiaowen Liu, Thuy Vien, Jingjing Duan, Shu-Hsien Sheu, Paul G. DeCaen, David E. Clapham

Cadmium exposure inhibits branching morphogenesis and causes alterations consistent with HIF-1α inhibition in human primary breast organoids. Sabrina A. Rocco, Lada Koneva, Lauren Y. M. Middleton, Tasha Thong, Sumeet Solanki, Sarah Karram, Kowit Nambunmee, Craig Harris, Laura S. Rozek, Maureen A. Sartor, Yatrik M. Shah, Justin Colacino

Genomic Locus Modulating Corneal Thickness in the Mouse Identifies POU6F2 as a Potential Risk of Developing Glaucoma. Rebecca King, Felix L. Struebing, Ying Li, Jiaxing Wang, Allison Ashley Koch, Jessica Cooke Bailey, Puya Gharahkhan, Stuart MacGregor, R. Rand Allingham, Michael A. Hauser, Janey L. Wiggs, Eldon E. Geisert

Clonal analysis of newborn hippocampal dentate granule cell proliferation and development in temporal lobe epilepsy. Shatrunjai P. Singh, Candi L. LaSarge, Amen An, John J. McAuliffe, Steve C. Danzer

Evo-devo & evo

Hox genes pattern the primary body axis of an anthozoan cnidarian prior to gastrulation. Timothy Q. DuBuc, Thomas B. Stephenson, Amber N. Rock, Mark Q. Martindale

Gene regulatory network architecture in different developmental contexts influences the genetic basis of morphological evolution. Sebastian Kittelmann, Alexandra D. Buffry, Isabel Almudi, Marianne Yoth, Gonzalo Sabaris, Franziska A. Franke, Juan Pablo Couso, Maria D. S. Nunes, Nicolas Frankel, Jose Luis Gomez-Skarmeta, Jose Pueyo-Marques, Saad Arif, Alistair P. McGregor

Duplication and divergence of Sox genes in spiders. Christian L. B. Paese, Daniel J. Leite, Anna Schoenauer, Alistair P. McGregor, Steven Russell

Pervasive correlated evolution in gene expression shapes cell type transcriptomes. Cong Liang, Jacob M. Musser, Alison Cloutier, Richard Prum, Gunter Wagner

How morphological development can guide evolution. Sam Kriegman, Nick Cheney, Josh Bongard

Developmental loci harbor clusters of accelerated regions that evolved independently in ape lineages. Dennis Kostka, Alisha K. Holloway, Katherine Pollard

Evolution and cell-type specificity of human-specific genes preferentially expressed in progenitors of fetal neocortex. Marta Florio, Michael Heide, Holger Brandl, Anneline Pinson, Sylke Winkler, Pauline Wimberger, Wieland B. Huttner, Michael Hiller

Developmental constraints on genome evolution in four bilaterian model species. Jialin Liu, Marc Robinson-Rechavi

The role of chromosomal inversions in speciation. Zachary Fuller, Christopher Leonard, Randee Young, Stephen Schaeffer, Nitin Phadnis

Gene regulatory network rewiring by an adaptively evolving microRNA cluster in Drosophila. Yang Lyu, Zhongqi Liufu, Juan Xiao, Yuxin Chen, Chung-I Wu, Tian Tang

Rapid evolution of gained essential developmental functions of a young gene via interactions with other essential genes. Yuh Chwen G Lee, Iuri M Ventura, Gavin R Rice, Don-Yuan Chen, Manyuan Long

The asexual genome of Drosophila. Stephan Schiffels, Ville Mustonen, Michael Lässig

Improved genome assembly and annotation for the rock pigeon (Columba livia). Carson Holt, Michael Campbell, David Keays, Nathaniel Edelman, Aurelie Kapusta, Emily Maclary, Eric Domyan, Alexander Suh, Wesley Warrenb, Mark Yandell, Thomas Gilbert, Michael D. Shapiro

Hemimetabolous genomes reveal molecular basis of termite eusociality. Mark C. Harrison, Evelien Jongepier, Hugh M. Robertson, Nicolas Arning, Tristan Bitard-Feildel, Hsu Chao, Christopher P. Childers, Huyen Dinh, Harshavardhan Doddapaneni, Shannon Dugan, Johannes Gowin, Carolin Greiner, Yi Han, Haofu Hu, Daniel S. T. Hughes, Ann-Kathrin Huylmans, Carsten Kemena, Lukas P. M. Kremer, Sandra L. Lee, Alberto Lopez-Ezquerra, Ludovic Mallet, Jose M. Monroy-Kuhn, Annabell Moser, Shwetha C. Murali, Donna M. Muzny, Saria Otani, Maria-Dolors Piulachs, Monica Poelchau, Jiaxin Qu, Florentine Schaub, Ayako Wada-Katsumata, Kim C. Worley, Qiaolin Xie, Guillem Ylla, Michael Poulsen, Richard A. Gibbs, Coby Schal, Stephen Richards, Xavier Belles, Judith Korb, Erich Bornberg-Bauer

Insights into platypus population structure and history from whole-genome sequencing. Hilary C Martin, Elizabeth M Batty, Julie Hussin, Portia Westall, Tasman Daish, Stephen Kolomyjec, Paolo Piazza, Rory Bowden, Margaret Hawkins, Tom Grant, Craig Moritz, Frank Grutzner, Jaime Gongora, Peter Donnelly

Reduction in major transcription factor binding domain families during the evolution of the avian lineage. Allie M. Graham, Jason S. Presnell

Host shifts result in parallel genetic changes when viruses adapt to closely related species. Ben Longdon, Jonathan P Day, Joel M Alves, Sophia CL Smith, Thomas M Houslay, John E McGonigle, Lucia Tagliaferri, Francis M Jiggins

Overlooked polyploidies in lycophytes generalize their roles during the evolution of vascular plants. Jinpeng Wang, Jigao Yu, Pengchuan Sun, Chao Li, Xiaoming Song, Tianyu Lei, Yuxian Li, Jiaqing Yuan, Sangrong Sun, Hongling Ding, Xueqian Duan, Shaoqi Shen, Yanshuang Shen, Jing Li, Fanbo Meng, Yangqin Xie, Jianyu Wang, Yue Hou, Jin Zhang, Xianchun Zhang, Xiyin Wang

A primitive starfish ancestor from the Early Ordovician of Morocco reveals the origin of crown group Echinodermata. Aaron W. Hunter, Javier Ortega-Hernandez

Russian Doll Genes and Complex Chromosome Rearrangements in Oxytricha trifallax. Jasper Braun, Lukas Nabergall, Rafik Neme, Laura F Landweber, Masahico Saito, Natasha Jonoska

Nearly Neutral Evolution Across the Drosophila melanogaster Genome. David Castellano, Jennifer James, Adam Eyre-Walker

Cell biology

Formation and disassembly of a contractile actomyosin network mediates content release from large secretory vesicles. Dagan Segal, Assaf Zaritsky, Eyal D. Schejter, Ben Zion Shilo

Variation in traction forces during cell cycle progression. Benoit Vianay, Fabrice Senger, Simon Alamos, Maya Anjur-Dietrich, Elizabeth Bearce, Bevan Cheeseman, Lisa Lee, Manuel Thery

Cell size control driven by the circadian clock and environment in cyanobacteria. Bruno M. C. Martins, Amy K. Tooke, Philipp Thomas, James C. W. Locke

RodZ promotes MreB polymer formation and curvature localization to determine the cylindrical uniformity of E. coli shape. Randy M Morgenstein, Benjamin P Bratton, Joshua W Shaevitz, Zemer Gitai

Giant flagellins form thick flagellar filaments in two species of marine Gammaproteobacteria. Nicholas Maitland Thomson, Josie L Ferreira, Teige R Matthews-Palmer, Morgan Beeby, Mark J Pallen

Uncoupling Intraflagellar Transport and Primary Cilia Formation Demonstrates Deep Integration of IFT in Hedgehog Signaling. Thibaut Eguether, Fabrice P Cordelieres, Gregory J Pazour

CDC20B is required for deuterosome-mediated centriole production in multiciliated cells. Diego R. Revinski, Laure-Emmanuelle Zaragosi, Camille Boutin, Sandra Ruiz-Garcia, Marie Deprez, Olivier Rosnet, Virginie Thome, Olivier Mercey, Agnes Paquet, Nicolas Pons, Brice Marcet, Laurent Kodjabachian, Pascal Barbry

Structural centrosome aberrations promote non-cell-autonomous invasiveness. Olivier Ganier, Dominik Schnerch, Philipp Oertle, Roderick Y. H. Lim, Marija Plodinec, Erich A. Nigg

A robust and tunable mitotic oscillator in artificial cells. Ye Guan, Zhengda Li, Shiyuan Wang, Patrick M. Barnes, Xuwen Liu, Haotian Xu, Minjun Jin, Allen P. Liu, Qiong Yang

Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore. Xun Bao, Christos Spanos, Tomoko Kojidani, Eric Lynch, Juri Rappsilber, Yasushi Hiraoka, Tokuko Haraguchi, Kenneth Sawin

Endocytosis caused by liquid-liquid phase separation of proteins. Louis-Philippe Bergeron-Sandoval, Hossein Khadivi Heris, Adam G. Hendricks, Allen J. Ehrlicher, Paul Francois, Rohit V. Pappu, Stephen W. Michnick

Systematic analysis of the molecular architecture of endocytosis reveals a nanoscale actin nucleation template that drives efficient vesicle formation. Markus Mund, Johannes Albertus van der Beek, Joran Deschamps, Serge Dmitrieff, Jooske Louise Monster, Andrea Picco, Francois Nedelec, Marko Kaksonen, Jonas Ries

The contributions of the actin machinery to endocytic membrane bending and vesicle formation. Andrea Picco, Wanda Kukulski, Hetty E. Manenschijn, Tanja Specht, John A. G. Briggs, Marko Kaksonen

CYRI (FAM49) proteins are local inhibitors of Scar/WAVE induced lamellipodia that bind directly to active Rac1. Loic Fort, Jose Batista, Peter A Thomason, Heather J Spence, Jennifer Greaves, Kirsty J Martin, Kurt I Anderson, Peter Brown, Sergio Lilla, Matthwe P Neilson, Petra Tafelmeyer, Sara Zanivan, Shehab Ismail, Nicholas C.O. Tomkinson, Luke H Chamberlain, Robert H Insall, Laura M Machesky

Dynein dynamics at the microtubule plus-ends and cortex during division in the C. elegans zygote. Ruddi Rodriguez-Garcia, Laurent Chesneau, Sylvain Pastezeur, Julien Roul, Marc Tramier, Jacques Pecreaux

The tumor suppressor APC is an attenuator of spindle-pulling forces during C. elegans asymmetric cell division. Kenji Sugioka, Lars-Eric Fielmich, Kota Mizumoto, Bruce Bowerman, Sander van den Heuvel, Akatsuki Kimura, Hitoshi Sawa

Dissecting single cell molecular spatiotemporal mobility and clustering at Focal Adhesions in polarised cells by fluorescence fluctuation spectroscopy methods. Jorge Bernardino de la Serna, Esther Garcia

Stopping Transformed Growth with Cytoskeletal Proteins: Turning a Devil into an Angel. Bo Yang, Haguy Wolfenson, Naotaka Nakazawa, Shuaimin Liu, Junqiang Hu, Michael Sheetz

Modelling

Model reduction permits Turing instability analysis of arbitrary reaction-diffusion models. Stephen Smith, Neil Dalchau

The phenomenon of growing surface interference explains the rosette pattern of jaguar. Michäel Dougoud, Christian Mazza, Beat Schwaller, Laszlo Pecze

Dynamic gradient scaling as a critical point of growth control. Daniel Aguilar Hidalgo, Steffen Werner, Ortrud Wartlick, Marcos González-Gaitán, Benjamin Friedrich, Frank Jülicher

Temporal precision of regulated gene expression. Shivam Gupta, Julien Varennes, Hendrik C. Korswagen, Andrew Mugler

A biophysical model explains the spontaneous bursting behavior in the developing retina. Dora Karvouniari, Lionel Gil, Olivier Marre, Serge Picaud, Bruno Cessac

An efficient gene regulatory network inference algorithm for early Drosophila melanogaster embryogenesis. Hirotaka Matsumoto, Hisanori Kiryu, Yasuhiro Kojima, Suguru Yaginuma, Itoshi Nikaido

Turbulent dynamics of epithelial cell cultures. C. Blanch-Mercader, V. Yashunsky, S. Garcia, G. Duclos, L. Giomi, P. Silberzan

Mechanical characterisation of disordered and anisotropic cellular monolayers. Alexander Nestor-Bergmann, Emma Johns, Sarah Woolner, Oliver E. Jensen

Do cells sense time by number of divisions? Zeev Schuss, Kimsy Tor, David Holcman

Euplotid: A quantized geometric model of the eukaryotic cell. Diego Borges-Rivera

Noise-driven Cell Differentiation and the Emergence of Organization. Hadiseh Safdari, Ata Kalirad, Cristian Picioreanu, Rouzbeh Tusserkani, Mehdi Sadeghi

A biophysical dynamic module for the polarisation of auxin efflux carriers PIN-FORMED (PIN). Valeria Hernandez-Hernandez, Rafael A. Barrio, Mariana Benitez, Naomi Nakayama, Jose Roberto Romero-Arias, Carlos Villarreal

Discrete and continuum approximations for collective cell migration in a scratch assay with cell size dynamics. Oleksii M Matsiaka, Catherine Penington, Ruth E Baker, Matthew Simpson

Shaping Epigenetic Memory via Genomic Bookmarking. Davide Michieletto, Michael Chiang, Davide Coli, Argyris Papantonis, Enzo Orlandini, Peter R. Cook, Davide Marenduzzo

Subtle alteration in microRNA dynamics accounts for differential nature of cellular proliferation. Dola Sengupta, Vinodhini Govindaraj, Sandip Kar

Mathematics at the eve of a historic transition in biology. Guo-Wei Wei

Tools & resources

| Imaging etc.

EpiGraph: an open-source platform to quantify epithelial organization. Pablo Vicente-Munuera, Pedro Gomez-Galvez, Antonio Tagua, Marta Letran, Yanlan Mao, Luis M. Escudero

An adaptable chromosome preparation methodology for use in invertebrate research organisms. Longhua Guo, Alice Accorsi, Shuonan He, Carlos Guerrero-Hernández, Shamilene Sivagnanam, Sean McKinney, Matthew Gibson, Alejandro Sánchez Alvarado

Combined flow cytometry and high throughput image analysis for the study of essential genes in Caenorhabditis elegans. Blanca Hernando-Rodríguez, Annmary Paul Erinjeri, María Jesús Rodríguez-Palero, Val Millar, Sara González-Hernández, María Olmedo, Bettina Schulze, Ralf Baumeister, Manuel J. Muñoz, Peter Askjaer, Marta Artal-Sanz

A method to keep the excitation light sheet in focus in selective plane illumination microscopy. Liang Gao

Topography and refractometry of sperm cells using SLIM. Lina Liu, Mikhail E Kandel, Marcello Rubessa, Sierra Schreiber, Mathew Wheeler, Gabriel Popescu

Simultaneously measuring image features and resolution in live-cell STED images. Andrew E. S. Barentine, Lena K. Schroeder, Michael Graff, David Baddeley, Joerg Bewersdorf

3D label-free imaging and analysis of Pinus pollen grains using optical diffraction tomography. Geon Kim, SangYun Lee, Seungwoo Shin, YongKeun Park

Three dimensional cross-modal image inference: label-free methods for subcellular structure prediction. Chek Ounkomol, Daniel A. Fernandes, Sharmishtaa Seshamani, Mary M. Maleckar, Forrest Collman, Gregory R. Johnson

Optical crosstalk in SPAD arrays for high-throughput single-molecule fluorescence spectroscopy. Antonino Ingargiola, Maya Segal, Angelo Gulinatti, Ivan Rech, Ivan Labanca, Piera Maccagnani, Massimo Ghioni, Shimon Weiss, Xavier Michalet

Recording neural activity in unrestrained animals with 3D tracking two photon microscopy. Doycho Karagyozov, Mirna Mihovilovic Skanata, Amanda Lesar, Marc Gershow

A genetically encoded Ca2+ indicator based on circularly permutated sea anemone red fluorescent protein. Yi Shen, Hod Dana, Ahmed S. Abdelfattah, Ronak Patel, Jamien Shea, Rosana S. Molina, Bijal Rawal, Vladimir Rancic, Yu-Fen Chang, Lanshi Wu, Yingche Chen, Yong Qian, Matthew D. Wiens, Nathan Hambleton, Klaus Ballanyi, Thomas E. Hughes, Mikhail Drobizhev, Douglas S. Kim, Minoru Koyama, Eric R. Schreiter, Robert E. Campbell

A FRET based biosensor for measuring Gα13 activation in single cells. Marieke Mastop, Nathalie R. Reinhard, Cristiane R. Zuconelli, Fenna Terwey, Theodorus W. J. Gadella Sr., Jakobus van Unen, Merel J. W. Adjobo-Hermans, Joachim Goedhart

Understanding boundary effects and confocal optics enables quantitative FRAP analysis in the confined geometries of animal, plant, and fungal cells. James L Kingsley, Jeffrey P Bibeau, Iman Mousavi, Cem Unsal, Zhilu Chen, Xinming Huang, Luis Vidali, Erkan Tuzel

Multidimensional quantitative analysis of mRNA expression within intact vertebrate embryos. Vikas Trivedi, Harry M. T. Choi, Scott E. Fraser, Niles A. Pierce

Single-molecule fluorescent amplification of RNA using clampFISH probes. Sara H Rouhanifard, Margaret Dunagin, Ian A Mellis, Sareh Bayatpour, Orsolya Symmons, Allison Cote, Arjun Raj

An optimized pipeline for parallel image-based quantification of gene expression and genotyping after in situ hybridization. Tomasz Dobrzycki, Monika Krecsmarik, Florian Bonkhofer, Roger K Patient, Rui Monteiro

Quantitative methods to investigate the 4D dynamics of heterochromatic repair sites in Drosophila cells. Christopher P Caridi, Laetitia Delabaere, Harianto Tjong, Hannah Hopp, Devika Das, Frank Alber, Irene Chiolo

In vivo multiphoton fluorescence imaging with polymer dots. Ahmed M Hassan, Xu Wu, Jeremy W Jarrett, Shihan Xu, David R Miller, Jiangbo Yu, Evan P Perillo, Yen-Liang Liu, Daniel T Chiu, Hsin-Chih Yeh, Andrew K Dunn

Eukaryotically expressed encapsulins as orthogonal compartments for multiscale molecular imaging. Felix Sigmund, Christoph Massner, Philipp Erdmann, Anja Stelzl, Hannes Rolbieski, Helmut Fuchs, Martin Hrabe de Angelis, Mitul Desai, Sarah Bricault, Alan Jasanoff, Vasilis Ntziachristos, Juergen Plitzko, Gil Gregor Westmeyer

Brillouin microscopy, what is it really measuring? Pei-Jung Wu, Irina Kabakova, Jeffrey Ruberti, Joseph M. Sherwood, Iain E. Dunlop, Carl Paterson, Peter Török, Darryl R. Overby

REASSESSING THE REVOLUTIONS RESOLUTIONS. Marin van Heel, Michael Schatz

Simultaneous Determination of Protein Structure and Dynamics Using Cryo-Electron Microscopy. Massimiliano Bonomi, Riccardo Pellarin, Michele Vendruscolo

ShuTu: Open-Source Software for Efficient and Accurate Reconstruction of Dendritic Morphology. Dezhe Z. Jin, Ting Zhao, David Hunt, Rachel Pearcy, Ching-Lung Hsu, Nelson Spruston

Automated 3D Neuron Tracing with Precise Branch Erasing and Confidence Controlled Back-Tracking. Siqi Liu, Donghao Zhang, Yang Song, Hanchuan Peng, Weidong Cai

MICCS: A Fully Programmable Multipurpose Integrated Cell Culture System. Timothy Kassis, Paola M. Perez, Chloe J. W. Yang, Luis R. Soenksen, David L. Trumper, Linda G. Griffith

Visual Representation of Experimental Protocols. James Scott-Brown, Antonis Papachristodoulou

Protein structures as shapes: Analysing protein structure variation using geometric morphometrics. Jose Sergio Hleap, Christian Blouin

Which line to follow? The utility of different line-fitting methods to capture the mechanism of morphological scaling. Alexander W. Shingleton

A Cautionary Tail: Changes in Integrin Behavior with Labeling. Catherine G. Galbraith, Michael W. Davidson, James A. Galbraith

Exploring biological networks in 3D, stereoscopic 3D and immersive 3D with iCAVE. Selim Kalayci, Zeynep H. Gumus

Quantitative imaging of chromatin decompaction in living cells. Elisa Dultz, Roberta Mancini, Guido Polles, Pascal Vallotton, Frank Alber, Karsten Weis

| Genome tools

CRISPys: Optimal sgRNA design for editing multiple members of a gene family using the CRISPR system. Gal Hyams, Shiran Abadi, Adi Avni, Eran Halperin, Eilon Shani, Itay Mayrose

Potential high-frequency off-target mutagenesis induced by CRISPR/Cas9 in Arabidopsis and its prevention. Qiang Zhang, Hui-Li Xing, Zhi-Ping Wang, Hai-Yan Zhang, Fang Yang, Xue-Chen Wang, Qi-Jun Chen

CRISPR-Cas12a target binding unleashes single-stranded DNase activity. Janice S Chen, Enbo Ma, Lucas B Harrington, Xinran Tian, Jennifer A Doudna

SgTiler: a fast method to design tiling sgRNAs for CRISPR/Cas9 mediated screening. Musaddeque Ahmed, Housheng Hansen He

Easy quantification of template-directed CRISPR/Cas9 editing. Eva Karina Brinkman, Arne Nedergaard Kousholt, Tim Harmsen, Christ Leemans, Tao Chen, Jos Jonkers, Bas van Steensel

Covalent linkage of the DNA repair template to the CRISPR/Cas9 complex enhances homology-directed repair. Natasa Savic, Femke Ringnalda, Katja Bargsten, Yizhou Li, Christian Berk, Jonathan Hall, Dario Neri, Martin Jinek, Gerald Schwank

Rapid, modular, and cost-effective generation of donor DNA constructs for CRISPR-based gene knock-in. Yi-Jiun Chen, Weikang Wang, Xiao-Jiun Tian, Daniel E. Lefever, David A. Taft, Jianhua Xing

Transgenic mouse lines expressing the 3xFLAG-dCas9 protein for enChIP analysis. Toshitsugu Fujita, Fusako Kitaura, Asami Oji, Naoki Tanigawa, Miyuki Yuno, Masahito Ikawa, Ichiro Taniuchi, Hodaka Fujii

A suite of transgenic driver and reporter mouse lines with enhanced brain cell type targeting and functionality. Tanya L Daigle, Linda Madisen, Travis A Hage, Matthew T Valley, Ulf Knoblich, Rylan S Larsen, Marc M Takeno, Lawrence Huang, Hong Gu, Rachael Larsen, Maya Mills, Alice Bosma-Moody, La’Akea Siverts, Miranda Walker, Lucas T Graybuck, Zizhen Yao, Olivia Fong, Emma Garren, Garreck Lenz, Mariya Chavarha, Julie Pendergraft, James Harrington, Karla E Hirokawa, Julie A Harris, Medea McGraw, Douglas R Ollerenshaw, Kimberly Smith, Baker A Baker, Jonathan T Ting, Susan M Sunkin, Jerome Lecoq, Michael Z Lin, Edward S Boyden, Gabe J Murphy, Nuno da Costa, Jack Waters, Lu Li, Bosiljka Tasic, Hongkui Zeng

A versatile genetic tool for post-translational control of gene expression in Drosophila melanogaster. Sachin Sethi, Jing W. Wang

Saturating Single-Cell Datasets. Aparna Bhaduri, Tomasz J. Nowakowski, Alex A. Pollen, Arnold R. Kriegstein

Comparison of whole-genome bisulfite sequencing library preparation strategies identifies sources of biases affecting DNA methylation data. Nelly Olova, Felix Krueger, Simon Andrews, David Oxley, Rebecca V Berrens, Miguel R Branco, Wolf Reik

Rapid high-resolution measurement of DNA replication timing by droplet digital PCR. Dzmitry G. Batrakou, Emma D. Heron, Conrad A. Nieduszynski

Improving Gene Regulatory Network Inference by Incorporating Rates of Transcriptional Change.Jigar Desai, Ryan C. Sartor, Lovely Mae Lawas, Krishna S. V. Jagadish, Colleen J. Doherty

Removing unwanted variation between samples in Hi-C experiments. Kipper Fletez-Brant, Yunjiang Qiu, David U Gorkin, Ming Hu, Kasper D Hansen

Binless normalization of Hi-C data provides significant interaction and difference detection independently of resolution. Yannick G. Spill, David Castillo, Marc A. Marti-Renom

Leveraging multiple transcriptome assembly methods for improved gene structure annotation. Luca Venturini, Shabhonam Caim, Gemy Kaithakottil, Daniel Lee Mapleson, David Swarbreck

Spliceosome profiling visualizes the operations of a dynamic RNP in vivo at nucleotide resolution. Jordan Burke, Adam Longhurst, Daria Merkurjev, Jade Sales-Lee, Beiduo Rao, James Moresco, John Yates III, Jingyi Jessica Li, Hiten D Madhani

Transcriptome-wide analysis of the functional intronome using spliceosome profiling. Weijun Chen, Jill Moore, Hakan Ozadam, Hennady P Shulha, Nicholas Rhind, Zhiping Weng, Melissa J. Moore

TF2Network: predicting transcription factor regulators and gene regulatory networks in Arabidopsis using publicly available binding site information. Shubhada R. Kulkarni, Dries Vaneechoutte, Jan Van de Velde, Klaas Vandepoele

FateID infers cell fate bias in multipotent progenitors from single-cell RNA-seq data. Josip Stefan Herman, Sagar Sagar, Dominic Grun

Cross-Site Comparison of Ribosomal Depletion Kits for Illumina RNAseq Library Construction. Zachary T Herbert, Jamie P Kershner, Vincent L Butty, Jyothi Thimmapuram, Sulbha Choudhari, Yuriy O Alekseyev, Jun Fan, Jessica W Podnar, Edward Wilcox, Jenny Gipson, Allison Gillaspy, Kristen Jepsen, Sandra Splinter BonDurant, Krystalynne Morris, Maura Berkeley, Ashley LeClerc, Stephen D. Simpson, Gary Sommerville, Leslie Grimmett, Marie Adams, Stuart S. Levine

An interlaboratory study of complex variant detection. Stephen E Lincoln, Justin M Zook, Shimul Chowdhury, Shazia Mahamdallie, Andrew Fellowes, Eric W Klee, Rebecca Truty, Catherine Huang, Farol L Tomson, Megan H Cleveland, Peter M Vallone, Yan Ding, Sheila Seal, Wasanthi DeSilva, Russell K Garlick, Marc Salit, Nazneen Rahman, Stephen F Kingsmore, Swaroop Aradhya, Robert L Nussbaum, Matthew J Ferber, Brian H Shirts

MEGAN-LR: New algorithms allow accurate binning and easy interactive exploration of metagenomic long reads and contigs. Daniel Huson, Benjamin Albrecht, Caner Bagci, Irina Bessarab, Anna Gorska, Dino Jolic, Rohan B.H. Williams

CREAM: Clustering of genomic REgions Analysis Method. Seyed Ali Madani Tonekaboni, Parisa Mazrooei, Victor Kofia, Benjamin Haibe-Kains, Mathieu Lupien

The fractured landscape of RNA-seq alignment: The default in our STARs. Sara Ballouz, Alexander Dobin, Thomas R Gingeras, Jesse Gillis

miRAW: A deep learning approach to predict miRNA targets by analyzing whole miRNA transcripts. Albert Pla Planas, Xiangfu Zhong, Simon Rayner

Classifying cells with Scasat – a tool to analyse single-cell ATAC-seq. Syed Murtuza Baker, Connor Rogerson, Andrew Hayes, Andrew D. Sharrocks, Magnus Rattray

scmap – A tool for unsupervised projection of single cell RNA-seq data. Vladimir Yu. Kiselev, Andrew Yiu, Martin Hemberg

Expressed Exome Capture Sequencing (EecSeq): a method for cost-effective exome sequencing for all organisms with or without genomic resources. Jonathan B Puritz, Kathleen E Lotterhos

Tn5Prime, a Tn5 based 5′ Capture Method for Single Cell RNA-seq. Charles Cole, Ashley Byrne, Anna E. Beaudin, E. Camilla Forsberg, Christopher Vollmers

Mantis: A Fast, Small, and Exact Large-Scale Sequence Search Index. Prashant Pandey, Fatemeh Almodaresi, Michael A. Bender, Michael Ferdman, Rob Johnson, Rob Patro

SpatialDE – Identification of spatially variable genes. Valentine Svensson, Sarah A. Teichmann, Oliver Stegle

Technology-independent estimation of cell type composition using differentially methylated regions. Stephanie C. Hicks, Rafael A. Irizarry

Revisiting criteria for plant miRNA annotation in the era of big data. Michael J. Axtell, Blake C. Meyers

OMGene: Mutual improvement of gene models through optimisation of evolutionary conservation. Michael Dunne, Steven Kelly

Research practice

Community-driven data analysis training for biology. Bérénice Batut, Saskia Hiltemann, Andrea Bagnacani, Dannon Baker, Vivek Bhardwaj, Clemens Blank, Anthony Bretaudeau, Loraine Guéguen, Martin Čech, John Chilton, Dave Clements, Olivia Doppelt-Azeroual, Anika Erxleben, Mallory Freeberg, Simon Gladman, Youri Hoogstrate, Hans-Rudolf Hotz, Torsten Houwaart, Pratik Jagtap, Delphine Lariviere, Gildas Le Corguillé, Thomas Manke, Fabien Mareuil, Fidel Ramírez, Devon Ryan, Florian Sigloch, Nicola Soranzo, Joachim Wolff, Pavankumar Videm, Markus Wolfien, Aisanjiang Wubuli, Dilmurat Yusuf, Rolf Backofen, Anton Nekrutenko, Björn Grüning

How Changes in Common Practice Can Improve the Quality of Biomedical Science. Matthias Steinfath, Silvia Vogl, Norman Violet, Franziska Schwarz, Hans Mielke, Thomas Selhorst, Matthias Greiner, Gilbert Schoenfelder

The impact factor fallacy. Frieder Michel Paulus, Nicole Cruz, Soeren Krach

Explanation implies causation? Leslie Myint, Jeffrey T. Leek, Leah R. Jager

Assessing value of biomedical digital repositories. Chun-Nan Hsu​, Anita Bandrowski, Jeffrey S. Grethe, Maryann E. Martone

Manipulating the alpha level cannot cure significance testing – comments on “Redefine statistical significance”. Trafimow D, Amrhein V, Areshenkoff CN, Barrera-Causil C, Beh EJ, Bilgiç Y, Bono R, Bradley MT, Briggs WM, Cepeda-Freyre HA, Chaigneau SE, Ciocca DR, Carlos Correa J, Cousineau D, de Boer MR, Dhar SS, Dolgov I, Gómez-Benito J, Grendar M, Grice J, Guerrero-Gimenez ME, Gutiérrez A, Huedo-Medina TB, Jaffe K, Janyan A, Karimnezhad A, Korner-Nievergelt F, Kosugi K, Lachmair M, Ledesma R, Limongi R, Liuzza MT, Lombardo R, Marks M, Meinlschmidt G, Nalborczyk L, Nguyen HT, Ospina R, Perezgonzalez JD, Pfister R, Rahona JJ, Rodríguez-Medina DA, Romão X, Ruiz-Fernández S, Suarez I, Tegethoff M, Tejo M, van de Schoot R, Vankov I, Velasco-Forero S, Wang T, Yamada Y, Zoppino FC, Marmolejo-Ramos F.

Key steps to avoiding artistry with significance tests. C Patrick Doncaster, Thomas H G Ezard

If funders and libraries subscribed to open access: The case of eLife, PLOS, and BioOne. Willinsky J, Rusk M.

Oxford Nanopore sequencing in a research-based undergraduate course. Yi Zeng, Christopher Herbert Martin

Why not…

Dietary and behavioral inferences from dental pathology and non-masticatory wear on dentitions from a British medieval town. Ian Towle, Carole Davenport, Joel Irish, Isabelle De Groote

Cobwebbing in the city: urbanization-driven changes in web-building are decoupled from body size in an orb-web spider. Maxime Dahirel, Maarten De Cock, Pieter Vantieghem, Dries Bonte

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A 3-year PhD fellowship in evolutionary developmental biology and genomics is available in the lab of Michalis Averof, at the Institut de Génomique Fonctionnelle de Lyon (IGFL) in France. The fellowship is funded by the Marie Curie ITN programme EvoCELL.

Some animals have the ability to regenerate parts of their body (limbs, tail, internal organs) after severe injury. However the molecular and cellular mechanisms underlying the regeneration of such complex organs are still poorly understood. The project will investigate cell differentiation during leg regeneration in the crustacean ​Parhyale hawaiensis, an emerging model for limb regeneration. The PhD fellow will determine the spectrum of cell types present in Parhyale limbs, their molecular profiles, and whether that diversity of cell types is fully restored after regeneration. In collaboration with other teams of the EvoCELL network, s/he will compare the transcriptional profiles of diverse cells types across phyla, in an effort to identify the evolutionary origins and conserved molecular signatures of progenitor cells.

The student will be trained in various technologies to analyze limb regeneration in Parhyale and compare it to regeneration in other species. S/he will use single-cell transcriptomics to establish the exhaustive repertoire of cell types prior to, during and after regeneration. S/he will participate in all steps of the experiment: dissociate limb cells, prepare libraries and computationally analyze the data. The fellow will also be trained in transgenesis, confocal microscopy and in situ hybridization in order to validate the identity of the detected cell populations and use markers to follow the fate of those cells during regeneration. This work will involve short periods of training/research in the laboratories of other EvoCELL partners and collaborators, and participation in yearly meetings and practical courses organized by the network, to take full advantage of the wide range of expertise available in EvoCELL.

The host lab (https://averof-lab.org) is based in the IGFL – an institute co-founded by the École Normale Supérieure de Lyon and the CNRS, whose scientific focus lies at the interface of developmental biology, functional genomics and evolution (http://igfl.ens-lyon.fr/). The lab’s working language is English. The fellow will be co-supervised by Michalis Averof and Mathilde Paris.

Applicants should have a Masters degree or equivalent (e.g. a 5-year university degree) to be eligible to embark on a PhD at the École Normale Supérieure de Lyon. To be eligible for the fellowship, candidates must be within the first four years of their research career and not hold a doctoral degree. Candidates of all nationalities may apply, but they must not have resided or carried out their main activity (work, studies, etc.) in France for more than 12 months in the 3 years immediately prior to their appointment (short stays such as holidays or compulsory national service are not taken into account).

The suggested starting date for the PhD is October 1, 2018.

Applicants should send a short letter of interest and CV to michalis.averof@ens-lyon.fr, and ask two referees to send recommendation letters to the same electronic address. The closing date for applications is February 2, 2018.

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Alzu’bi A, Lindsay SJ, Harkin LF, McIntyre J, Lisgo SN, Clowry GJ (2017) The transcription factors COUP-TFI and COUP-TFII have distinct roles in arealisation and GABAergic interneuron specification in the early human fetal telencephalon. Cerebral Cortex 27: 4677-4690.

One author’s perspective on the origins of this study (Gavin Clowry)

For me the origins of this research paper stretch back nearly twenty years. I was part of a research group, led by the paediatric neurologist Professor Janet Eyre, studying the neurobiology of cerebral palsy including neurophysiological studies on infants and children. A little boy with hemiplegia generated some remarkable results. He was unusual in that he had suffered a brain lesion relatively early in development compared to most CP sufferers, around mid-gestation, resulting in destruction of the sensorimotor cortex unilaterally. Transcranial magnetic stimulation, coupled with electromyographic recording, showed that muscles contralateral to the lesion were strongly responsive to stimulation of the ipsilateral motor cortex, not unusual in hemiplegics. What was unusual, though, was the strong response of the same muscles to stimulation of the intact contralateral occipital cortex. Ten more years of experiments and imaging were required to confirm these observations [1] but it was shown that in response to the lesion, visual cortex had acquired or maintained projections to motor centres in the spinal cord (Figure 1).

This set us speculating on the nature and plasticity of the protomap in human. Around this time strong evidence was being presented in favour of the protomap hypothesis originally proposed by Pasko Rakic [2]. The hypothesis stated that the organisation of the cerebral cortex into functional areas is determined by the co-ordinated and compartmented expression of genes in time and space at the earliest stages of its development, prior to its connection with the sensory input that could drive its maturation. Experiments in mice (Figure 2) [3, 4] were showing that altered gradients of transcription factor expression across the early cortex in mutant and transgenic mice led to an altered functional map for primary cortical areas. But does all this hold true for human development? For our next programme of research we teamed up with Prof Susan Lindsay and the Human Developmental Biology Resource to explore gene expression in the early stages of human cortex development especially to look for evidence for a human protomap.

Our first success was to show that the transcription factors PAX6 and EMX2 form counter-gradients across the human cortex, just as they do in mouse, but only at the very earliest stages of cortical plate formation (Figure 3) [6]. Unlike in mouse, where expression is confined to progenitor cells, EMX2 was found to be expressed in a gradient in the post-mitotic neurons of the cortical plate as well.  We also found arealised expression for other genes, by histological techniques, from quantitative measurements of mRNA expression, and in fetal cells cultured from different cortical regions [7, 8]. For instance, the layer V specific transcription factor CTIP2, along with transmembrane signalling molecules and corticospinal tract markers ROBO1 and SRGAP1, are more highly expressed in the frontal cortex between 9-12 PCW which might represent the predominance of corticofugal projection neurons in frontal sensorimotor areas.

However the crucial question is whether such a developmental scheme observed in rodents is sufficient to produce all the extra areas of specialised association cortex, along with the vastly increased interconnectivity between these areas, seen in primates [9]? We believe our latest study may shed some light on this question [10]. We studied expression patterns of the arealising transcription factors COUP-TFI, COUP-TFII and SP8. What was noticeable in humans was that SP8 and COUP-TFI overlap extensively in the ventricular zone of visual, auditory and somatosensory cortex. This differs from the mouse in which COUP-TFI and SP8 show little overlap. Combinatorial  expression of COUP-TFI and SP8 could maintain a common genetic identity for future primary sensory areas (visual, auditory and somatosensory) and a partially shared identity with SP8-expressing frontal motor cortex with which these sensory areas will interconnect, along with allied association cortex, via dorsal sensorimotor pathways. In mouse COUP-TFII is confined to a very small portion of the posterior cortex but in human is expressed extensively throughout the ventral temporal  and ventral posterior cortex where it overlaps with COUP-TFI expression. Perhaps the expansion of cortical COUP-TFII expressing territory in human fetal brain mirrors the increased size and complexity of the association areas of the ventro-temporal cortex.  An extension of this observation is that dorsal and ventral hippocampus are also differentiated by combinatorial expression of SP8/COUP-TFI and COUP-TFII/COUP-TFI respectively. Each domain has distinct functions and distinct efferent and afferent connections. It appears that the protomap for human hippocampal specialisation is laid down early in development.

It has been a 15 year journey to reach the beautiful images in Figure 4 with many interesting diversions along the way; for instance, when studying PAX6 expression we discovered a new class of progenitor cell in the subventricular zone of the cortex [11] which was subsequently shown to be a new class of radial glia [12]. We now know that humans as well as rodents have a protomap to guide cortical development, but this protomap is plastic and can be perturbed by genetic alteration, pharmacological interventions and lesions. Although more investigation is needed, it seems highly likely that the protomap has evolved in complexity as the cerebral cortex has evolved in complexity, rather than entirely new mechanisms being required to shape the cortex’s functional organisation, although, as ever, more research is needed to test this assertion. Ensuring that neurons in the cortex have the right regional and functional identity is crucial to establishing their long and short range connectivity, deficits in which are proposed to underlie neurodevelopmental orders such as autism and schizophrenia, so there is good reason to extend this journey a while longer yet.

References

1.  Basu A, Graziadio S, Smith M, Clowry GJ, Cioni G, Eyre JA (2010) Developmental plasticity connects visual cortex to motoneurons after stroke. Annals of Neurology 67:132-6.
2.  Rakic P (1988) Specification of cerebral cortical areas. Science 241:170.
3.  Bishop KM, Goudreau G, O’Leary DDM (2000) Regulation of area identity in the mammalian neocortex by Emx2 and Pax6. Science 288:344-9.
4.  Muzio L, Di Benedetto B, Stoykova A, Boncinelli E, Gruss P, Mallamaci A (2002) Emx2 and Pax6 control regionalization of the pre-neuronogenic cortical primordium. Cerebral Cortex 12:129-39.
5.  Clowry GJ, Alzu’bi A, Harkin LF, Sarma S, Kerwin J, Lindsay S (2017) Charting the protomap of the human telencephalon. Seminars in Cell and Developmental Biology, Epub ahead of print, doi.org/10.1016/j.semcdb.2017.08.33.
6.  Bayatti N, Sarma S, Shaw C, Eyre JA, Vouyiouklis DA, et al (2008) Progressive loss of PAX6, TBR2, NEUROD and TBR1 mRNA gradients correlates with translocation of EMX2 to the cortical plate during human cortical development. European Journal of Neuroscience 28: 1449-1456.
7.  Ip BK, Wappler I, Peters H, Lindsay S, Clowry GJ, Bayatti N (2010) Investigating gradients of gene expression involved in early human cortical development. Journal of Anatomy 217: 300-311.
8. Ip BK, Bayatti N, Howard NJ, Lindsay S, Clowry GJ (2011) The corticofugal neuron-associated genes ROBO1, SRGAP1, and CTIP2 exhibit an anterior to posterior gradient of expression in early fetal human neocortex development. Cerebral Cortex 21: 1395-1407.
9.  Buckner RL, Krienen FM (2013) The evolution of distributed association networks in the human brain. Trends in Cognitive Sciences 17: 648-65.
10.  Alzu’bi A, Lindsay SJ, Harkin LF, McIntyre J, Lisgo SN, Clowry GJ (2017) The transcription factors COUP-TFI and COUP-TFII have distinct roles in arealisation and GABAergic interneuron specification in the early human fetal telencephalon. Cerebral Cortex 27: 4677-4690.
11.  Bayatti N, Moss JA, Sun L, Ambrose P, Ward JFH, Lindsay S, Clowry GJ (2008) A molecular neuroanatomical study of the developing human neocortex from 8 to 17 postconceptional weeks revealing the early differentiation of the subplate and subventricular zone. Cerebral Cortex 18: 1536-1548.
12. Lui, J.H. Hansen, D.V., Kriegstein, A.R. 2011. Development and evolution of the human neocortex. Cell 146: 18–36.

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Positions are available to study the physical principles of morphogenesis in the Mechanics of Morphogenesis / Davidson Laboratory at the University of Pittsburgh in the Department of Bioengineering. Our group focuses on studying the molecular, cellular, and tissue-scale processes that regulate mechanical properties and force-production during morphogenesis. Projects can involve quantitative cell biology, biophysics, bioengineering, and embryology.

Postdoctoral candidates will have recently completed a PhD and have a background in either bioengineering, biophysics, cell and developmental biology, or cell- and tissue- mechanics. The research environment at the University of Pittsburgh includes a dynamic community of bioengineers, developmental biologists, cell- and tissue-level biomechanics, and theoretical biologists. Nearby resources include the Peterson Institute of NanoScience and Engineering and the Pittsburgh Supercomputing Center. Contemporary Pittsburgh is a diverse vibrant city undergoing a renaissance led by world class Universities and the University of Pittsburgh Medical Center. The University of Pittsburgh is an Equal Opportunity Employer. Women and minorities are especially encouraged to apply.

Interested applicants should forward their CV and statement of research interests to:

Lance Davidson (lad43@pitt.edu)
Professor of Bioengineering
University of Pittsburgh
mechmorpho.org

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Position Description:

The Marine Biological Laboratory seeks a Research Assistant II or III to join the laboratories of Kristin Gribble and David Mark Welch in the Josephine Bay Paul Center. The successful candidate will help develop genome editing techniques, including CRISPR/Cas9, in rotifers, a novel aquatic invertebrate model system for studies of aging, neurobiology, developmental biology, ecology, and evolution. Specific goals of the project include designing guide RNAs, optimizing microinjection methodologies, phenotyping and genotyping mutant strains, and screening genes of interest.

Qualifications:

Applicants should have a B.A., B.S., or Master’s degree in biology, cell/molecular biology, biochemistry, or a related field. This position requires proficiency and previous experience in basic molecular biology techniques, microscopy, microinjection, and CRISPR/Cas9 methodology. We are seeking an independent, organized, enthusiastic, and productive individual with robust problem solving skills. Excellent interpersonal skills, attention to detail, and a strong work ethic are essential. Position level and salary will depend upon education and experience. The ideal candidate will have working familiarity with RNAi and transgenic protocols. Proficiency in bioinformatics is a plus. Previous experience in established animal model or in non-model systems is preferred.

To apply: Visit http://www.mbl.edu/hr/employment/ 

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A Brain Research UK-sponsored research assistant position for a highly motivated scientist is available in the laboratory of Dr. Claudia Barros at the Peninsula School of Medicine of Plymouth University, UK. The project is an opportunity to characterise novel targets and its human orthologue genes potentially involved in brain tumour initiation and growth, which have been identified in our laboratory. Molecular biology, cellular and biochemical techniques will be employed, including gene loss and gain of function assays, FACS, RT-qPCR, immunochemistry, western-blotting and confocal imaging. Work will make use of human brain tumour cell lines, tumour tissues  and Drosophila brain as a model. A relevant 1^st class or 2:1 (or equivalent) Bachelor degree is required and a postgraduate research degree may be preferred. You must have experience in some of the mentioned techniques, in particular cell culture and tissue work, and a suitable background knowledge. Good analytical, organisational and presentation skills, ability to multitask and collaborate with team members, and a genuine dedication to the research work are essential. Please include a cover letter detailing suitability/ experience/ interest and an academic CV with your application, in addition to ensure that 1-2 academic references are received.

Full or part time; Fixed term: initially 7 months if full time; Salary start: £24,983/ year.

Closing date for applications: 1^st January 2018

Follow the link to apply:

https://hrservices.plymouth.ac.uk/tlive_webrecruitment/wrd/run/ETREC107GF.open?VACANCY_ID=5072839rf8&WVID=1602750fTZ&LANG=USA

Contact for informal discussion: claudia.barros@plymouth.ac.uk

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Understanding the first step in the formation of organismal complexity in the mouse embryo

 As biologists, we are very used to poking and prodding very complex systems, be it drosophila or homo sapiens. Rarely is it a prerogative to take a step back and really understand how such complexity arises seemingly out of nowhere. How is that we start off from a single cell and over a period as short as 48 hours (in the mouse at least) we already start seeing complexity arising?

In mice, a single-cell zygote undergoes a series of cleavage cell divisions and morphogenetic changes to form a unipotent epithelial vesicle termed the trophectoderm (TE) enclosing a compact group of pluripotent stem cells known as the inner cell mass (ICM) (Fig.1F).

 

 

Restriction of cell fate takes place over an extended time period of 48 hours from the 8-cell (morula) stage (Fig.1C), when all cells are indistinguishable from one another and are capable of forming all three germ layers. This feature of cells is termed totipotency and is a transient characteristic of embryonic stem cells before they commit to become either TE or ICM.

 

At this 8-cell stage compaction of the embryo begins, in which the embryo surface smoothens because of an increase in intercellular adhesion. Cells epithelialise, forming tight junctions (which acts as a seal) between cells, limiting diffusion and what you are left with is fluid-filled epithelial vesicle enclosing a small number of cells (Fig. 1D-F).

 

It is at point that the first commitment of cells occurs, whereby the outer epithelium (Fig.1E) becomes committed to form the trophectoderm (TE), which subsequently gives rise to the trophoblast layers of the placenta and the trophoblast giant cells. Whilst the small population of enclosed cells commit to becoming the ICM, which is the pluripotent stem cell lineage of the embryo, giving rise to all of the primary germ layers of the foetus and its extraembryonic tissue.

 

At this stage of development, protein synthesis from maternal mRNA becomes more transient as the embryo’s own gene programs begin to switch on. Once commitment occurs, as the morulae becomes a blastocyst, differential gene expression is seen between the ICM and TE. At day 2 ½ post-fertilisation, all cells within the morula uniformly express most genes, including the pluripotency factor Oct4 and the TE marker Cdx2. Interestingly, at day 3 ½ the first real differential gene expression is observed, where the ICM begins to express Oct4 whilst loosing its ability to express Cdx2 and conversely the trophectoderm begins to express Cdx2 whilst loosing all Oct4 activity. There is a mutual repression by Oct4 and Cdx2 which further consolidates the TE and ICM segregation.

 

Elucidating the mechanism governing a cell’s ability to become either a unipotent TE cell or a pluripotent stem cell of the ICM can open up new avenues for generating and maintaining pluripotency in vitro. In an attempt to understand this initial lineage segregation, a stem cell line was cultured which removes the Oct4 gene upon treatment with tamoxifen. This cell line also had a florescent tdTomato reporter under the control of a constitutive promoter, meaning that these cells fluoresce red when exposed to light in the blue to green range.

 

The following cells were cultured in serum-LIF (a differentiation permissive medium) and different portions of the cells were treated with tamoxifen for either 24, 48 or 92 hours to allow for the excision of the Oct4 gene. Once these time points of treatment were reached, cells were microinjected into live mouse morulae and blastocysts. Approximately 5 morulae and blastocysts were microinjected with 8-10 stem cells deficient in Oct4 from each time point as well as un-induced cells form the same batch as a control. These morulae were left for two days to allow for compaction and the first lineage segregation to occur. These were then promptly fixed and immunostained to examine what effect the deletion of Oct4 had on the cell fate choices that the injected stem cells made.

 

Following what we already know about what happens during development, it can be hypothesized that stem cells that do not have the capacity to make Oct4 will commit to the trophectoderm lineage as they are missing a key pluripotency factor and therefore cannot become pluripotent cells competent of forming all 3 germ layers.

 

Unfortunately due to rising temperatures in the laboratory during summer (the air conditioning was of course broken on the days the microinjections were performed), upon imaging it was clear that in most cases only 1 stem cell, out of the 8-10 injected, integrated into the embryo. This was prevalent in the un-induced cells also, suggesting that it was not the tamoxifen treatment that caused toxicity to the cells but rather the experimental conditions.  Integration rates were higher in morulae than in blastocysts as expected, since by the blastocyst stage cell commitment has already occurred making it harder for integration to ensue.

 

Out of the cells that did integrate, only 1 appeared to express Cdx2 markers showing that it has adopted a trophectodermal cell fate, whilst the others exhibited a mixture of pluripotency markers. The conclusion from this being that although Oct4 is necessary for cell commitment to the ICM lineage, additional molecular events must underpin this initial commitment in the mouse model. Inferring this from the data is difficult considering how the number of integrated stem cells was so low and future experiments with more tightly controlled conditions are advised.

 

These results however are concordant with other studies, with Wu and Schöler (2014) reporting that the “establishment of totipotency in maternal Oct4–depleted embryos was not affected, and that these embryos could complete full-term development without any obvious defect.” In addition to this, Wu and Schöler were able to form Oct4 expressing inner cell masses in embryos with complete inactivation of both maternal and zygotic Oct4 expression as well as reprogramming of fibroblasts into fully pluripotent cells by Oct4-deficient oocytes.

 

This, in conjunction with the results I obtained, tends to indicate that Oct4 is not essential for the initiation of pluripotency but in contrast to its role is critical for the maintenance of pluripotency.

 

I would like to thank Professor Jennifer Nichols, Ayaka Yanagida, Peter Baillie-Johnson, Thorsten Boroviak, Ken Jones, Tim Lohoff and everyone else at the Cambridge Stem Cell Institute for their invaluable guidance and support throughout my internship. I would also like to thank the British Society for Developmental Biology for granting me the Gurdon Studentship Award without which none of this would have been possible.

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Built into the side of a tree covered hill on a remote Japanese island  lies what at first sight appears to be a super-villain’s lair, or perhaps  the HQ of Jurassic Park. In fact we had arrived at the Okinawa Institute of Science and Technology (OIST) for their 2 week Developmental Neurobiology Course. DNC is a 2 week intensive lecture and lab based course designed to teach, inspire and foster collaborations between the next generation of developmental neurobiologists.

23 of us were accepted, a highly diverse collection of PhD students and Postdocs from all over the world to spend two weeks in paradise all there because of our love for developmental neurobiology. The course was split into two halves: Week one – lectures in the morning and a lab project in the afternoon. Week 2 – lecture bootcamp! 6-7 hours of fascinating lectures a day by some of the most distinguished researchers in the field on a vast variety of topics.

While the classes were intense there was plenty of downtime to interact, consolidate and simply think about the wider field beyond our individual specialities, with plenty of swimming off the beach attached to our accommodation! In this post I will try to summarise the course and hopefully explain why I think courses like this are so crucial for early career researchers to participate in.

Week 1:  

After 27 hours of travelling I finally arrived at our Seaside House accommodation.  OIST generously covered all course costs, accommodation, food and half of travel costs for all participants; a critical factor in making it accessible to early career researchers.

We started our first day with intensive short talks from all participants so we all knew a little bit about each other’s background. The range of specialities was huge, from pure molecular biologists to electrophysiologists, to using Zebrafish to study dyslexia, making for some fascinating discussions throughout the 2 week course.  We got the chance to learn more about each other’s research the following day, where after a fascinating lecture on microscopy by Ulrike Engel, we gathered for a poster session to present our research to staff and participants.

A key part of DNC is the opportunity to learn new techniques that we might not otherwise get the opportunity to learn. This was taught through a choice of one of five lab projects, but before committing we got a brief rotation in each lab to learn more. The five lab project options available to us were:

1. Analysis of Drosophila embryonic neuromuscular development
2. Ca imaging and electrophysiology recording from Drosophila Larvae
3. In utero electroporation in mouse
4. Live imaging of zebrafish nervous system
5. Electrophysiology in zebra finch auditory system

I was lucky enough to be taught in utero electroporatation in mouse by Hiroshi Kawasaki, a powerful technique for highly spatially specific gene editing during development.

Having been assigned our lab projects the week continued with lectures in the morning and lab projects in the afternoon. Our lectures were fascinating and varied:

Cecilia Moens (Fred Hutchinson) spoke about cranial motor neuron development in the Zebrafish.

Lisa Goodrich (Harvard) explained about the peripheral nervous system, focusing on cochlear development.

Hiroshi Kawasaki (Kanazawa University) told us about his research focused on the molecular mechanisms controlling cortical development.

Michael Granato (U Penn) talked about axon guidance and regeneration in Zebrafish.

For me the length (3 hours) of the lectures was key to the immersion of the course.  This time period gave the lecturers the chance to speak about their long research journey and all the side stories that would normally be left out of a shorter lecture. Although intense, every hour we were rewarded (behavioural conditioning?) with coffee and snacks, we had the opportunity to ask questions at any point, and the lecturers were able to enter into group discussions without fear of time constraints.

In the afternoons we utilised the fantastic laboratories at OIST to work on our lab projects with the help of our group leaders and the fantastic Postdoc tutors. Under their careful tuition we practised and perfected our techniques, and gathered our data to present at the end of the course. The resources available at OIST were staggering, we were able to perform CLARITY on our electroporated brains and image them with a light-sheet microscope, while the Drosophila group used super-resolution to image individual boutons in the Drosophila larvae!

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Lab projects complete, we celebrated the end of the first week with a barbecue and fireworks at Seaside House, and of course Japanese karaoke with the course organisers!!

Week 2: Lecture Bootcamp!!

Before the intensive days of lectures started, we were given a day off to recuperate and explore Okinawa. For a couple of us that meant a relaxing trip to an Onsen, for others Scuba-Diving, and for one adventurous group it involved a multi-stop tour to a pineapple farm, a Dragonball Z-themed butterfly park (…?) and the Okinawa aquarium.

Re-energised after our free day we threw ourselves into the second week of lectures, learning about ideas and concepts that we had never encountered in our day to day research:

Yimin Zou (UCSD) spoke about how we must understand the processes controlling axon guidance during development, to investigate how circuits may repair themselves following injury.

Jeff Wickens (OIST) gave a lecture on the neural mechanisms that underlie learning and adaptation in the mammalian brain.

Kang Shen (Stanford) talked about the molecular mechanisms behind dendrite patterning and how they wire into neural circuits.

Tomoyuki Takahashi (OIST) we were privileged to be given a lecture by one of the founders of electrophysiology,  a fact made clear by the massive increase in audience size as many OIST researchers came to hear him speak.

Mei Zhen ( University of Toronto)  described her research on understanding how the C.elegans neural motor system translates into movement.

Greg Basaw (U Penn) gave as another axon guidance lecture, this time from the perspective of receptor regulation during Drosophila development.

Anne Hart (Brown) gave one of my favourite lectures as she described using a wide range of models from C.elegans to mice to study disease mechanisms in a highly interactive manner calling on us to think of research ideas.

That Friday afternoon we gave our brains a chance to consolidate as we were taken on an excursion to Shurijo Castle to experience more of the island’s rich history before enjoying a traditional Okinawa dinner with the course organisers and lecturers in the capital Naha.

The next day we received news, after several days of speculation, that there was a typhoon passing between the Okinawa prefecture and mainland Japan. OIST is built for this weather so we continued on with the course albeit with an embargo on all water activities.

Hitoshi Okamoto (Riken) gave a fascinating lecture on social conflict in Zebrafish and the role of the habenula in this. To me this was particularly interesting as I had never considered this behavioural use for the Zebrafish before.

Tadashi Isa (NIPS) gave our penultimate lecture on how networks reorganise to recover movements following spinal cord injury.

Yoko Yazaki-Sugiyama (OIST) delivered our final lecture on critical periods in Zebra Finch auditory systems during song learning.

As lectures concluded on the final day we concluded the academic side of the course by giving presentations on our lab projects from the first week. This gave us an excellent opportunity to show the skills we had developed, consolidate our knowledge and thank our teachers and tutors for their guidance and support.

We gathered for a final dinner together in Seaside house with traditional Okinawan entertainment as we ate. After dinner we had final words from the course organisers who presented us with certificates of our participation. This also gave us time to thank them extensively for all their work organising the course and providing us with the most incredible learning opportunity that will shape our careers as neurobiologists. We ended the course as a team, with fireworks and karaoke as the lightening storm from the typhoon raged around us.

This course is such a fantastic opportunity for young researchers. The vast diversity of lectures will broaden your horizons and bring new directions to your project and future plans. The people I met will be my friends and colleagues for the rest of my career and I hope one day I will get to publish alongside them as we collaborate together. I cannot thank the course organisers; Yoko Yazaki-Sugiyama, Ichiro Masai, David Van Vactor, Yimin Zou and Hiroshi Kohsaka enough for this opportunity as well as all the support staff who made it happen. I encourage all young developmental neurobiologists to apply to this wonderful course, you will not regret it!

Next stop: Wood’s Hole 2018!

(3 votes)

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