@article{d7f5f235ff6f440e8c6e13fbbb0963ae,
title = "Uncoupling of neurogenesis and differentiation during retinal development",
abstract = "Conventionally, neuronal development is regarded to follow a stereotypic sequence of neurogenesis, migration, and differentiation. We demonstrate that this notion is not a general principle of neuronal development by documenting the timing of mitosis in relation to multiple differentiation events for bipolar cells (BCs) in the zebrafish retina using in vivo imaging. We found that BC progenitors undergo terminal neurogenic divisions while in markedly disparate stages of neuronal differentiation. Remarkably, the differentiation state of individual BC progenitors at mitosis is not arbitrary but matches the differentiation state of post-mitotic BCs in their surround. By experimentally shifting the relative timing of progenitor division and differentiation, we provide evidence that neurogenesis and differentiation can occur independently of each other. We propose that the uncoupling of neurogenesis and differentiation could provide neurogenic programs with flexibility, while allowing for synchronous neuronal development within a continuously expanding cell pool.",
keywords = "bipolar cells, development, differentiation, neurogenesis, retina",
author = "Peter Engerer and Suzuki, {Sachihiro C.} and Takeshi Yoshimatsu and Prisca Chapouton and Nancy Obeng and Benjamin Odermatt and Williams, {Philip R.} and Thomas Misgeld and Leanne Godinho",
note = "Funding Information: We thank Kristina Wullimann for expert fish husbandry and Yvonne Hufnagel, Alexandra Graupner, and Monika Schetterer for expert technical and administrative support. We are especially grateful to Rachel Wong (U. Washington, Seattle), who generously supported this project in multiple ways, thanks to her, and Magdalena G{\"o}tz and Tim Czopka for critical reading of an earlier version of this manuscript. We are grateful to M. Nonet (Washington University in St. Louis) for the pCold Heart Tol2 vector, M. Meyer (King's College London) for the 5xUAS:TagRFP-T vector, T. Nicolson (Oregon Health & Science University and Vollum Institute) for the ribeye a cDNA template, R. K{\"o}ster (Technische Universit{\"a}t Braunschweig) for pSK5xUAS:Centrin2-YFP, and P. Raymond (University of Michigan) for the anti-Crx antibody. The mOrange2-PCNA-19-SV40NLS-4 plasmid was a gift from Michael Davidson (Addgene plasmid # 57971). We thank S. Higashijima (National Institutes of Natural Sciences, Okazaki Institute for Integrative Bioscience) for the Tg(vsx1:GFP)nns5 and Tg(vsx2:GFP)nns1 BAC transgenic lines which were generated with the support of the National Bioresource Project of Japan. We also thank R. Wong for providing the following transgenic lines: Tg(pax6-DF4:gap43-CFP)q01, Tg(vsx1:MCerulean)q19, Tg(14xUAS:MYFP), and Tg(crx:MA-CFP)q20, and L. Lagnado (University of Sussex, UK) for Tg(−1.8ctbp2a:mCherry-ctbp2a)lmb7. The Tg(−1.8ctbp2:gap43-EGFP)lmb1 line was made in the laboratory of L. Lagnado at MRC-LMB, Cambridge. This project was made possible by funding to L.G. and T.M. from the Deutsche Forschungsgemeinschaft (DFG) through Collaborative Research Center 870 “Assembly and Function of Neuronal Circuits”, project A11. T.M. is further supported by the Center for Integrated Protein Science Munich (CIPSM, EXC 114), the European Research Council under the European Union's Seventh Framework Program (FP/2007-2013; ERC Grant Agreement no. 616791), the Munich Center for Systems Neurology (SyNergy; EXC 1010), the DFG Priority Program 1710 (Mi694/4-1), the DFG research grants Mi694/7-1, 8-1, and the German-Israeli Foundation (I-1200-237.1/2012). T.M. is also associated with the German Center for Neurodegenerative Diseases (DZNE Munich). P.R.W. was supported by the Human Frontier Science Program and the Wings for Life Foundation. N.O. was supported by the Amgen Scholar program. S.C.S. and T.Y. were supported by a grant awarded to R. Wong (NIH EY14358). P.E. was supported by the DFG Research Training Group 1373 and the Graduate School of the Technische Universit{\"a}t M{\"u}nchen (TUM-GS). Publisher Copyright: {\textcopyright} 2017 The 1134 Authors. Published under the terms of the CC BY NC ND 4.0 license",
year = "2017",
month = may,
day = "2",
doi = "10.15252/embj.201694230",
language = "English",
volume = "36",
pages = "1134--1146",
journal = "EMBO Journal",
issn = "0261-4189",
number = "9",
}