@article{5b55cc4b9016453097fe1711a112f136,
title = "Coordinated control of neuronal differentiation and wiring by sustained transcription factors",
abstract = "The large diversity of cell types in nervous systems presents a challenge in identifying the genetic mechanisms that encode it. Here, we report that nearly 200 distinct neurons in the Drosophila visual system can each be defined by unique combinations of on average 10 continuously expressed transcription factors. We show that targeted modifications of this terminal selector code induce predictable conversions of neuronal fates that appear morphologically and transcriptionally complete. Cis-regulatory analysis of open chromatin links one of these genes to an upstream patterning factor that specifies neuronal fates in stem cells. Experimentally validated network models describe the synergistic regulation of downstream effectors by terminal selectors and ecdysone signaling during brain wiring. Our results provide a generalizable framework of how specific fates are implemented in postmitotic neurons.",
author = "{\"O}zel, {Mehmet Neset} and Gibbs, {Claudia Skok} and Isabel Holguera and Mennah Soliman and Richard Bonneau and Claude Desplan",
note = "Funding Information: We thank all members of the Desplan and Bonneau laboratories; O. Hobert, R. Mann, and D. Jabaudon for helpful discussions; C. Doe, S. Aerts, J. Blau, E. Mazzoni, R. Hiesinger, N. Konstantinides, D. Chen, R. Loker, and S. Mukherjee for critical reading of the manuscript; D. Krantz, I. Rebay, C.-T. Chien, W. Grueber, and J. Rister for reagents; Y.-C. Chen for help with plotting; J. Janssens and S. Aerts for sharing the snATAC-seq data ahead of publication; and G.-A. Saldi for help with network inference. This work was supported by the National Institutes of Health (NIH grants EY13010 and EY017916 to C.D. and R01HD096770, R01CA229235, and RM1HG011014 to R.B.) and the Simons Foundation. M.N.O. was a Leon Levy Neuroscience Fellow and is supported by the National Institute of Neurological Disorders and Stroke (NIH grant K99NS125117). C.S.G. is supported by National Science Foundation award 1922658 to the New York University Center for Data Science. I.H. has been supported by Human Frontier Science Program Postdoctoral Fellowship LT000757/2017-L and by a senior postdoctoral fellowship from the Kimmel Center for Stem Cell Biology. Publisher Copyright: {\textcopyright} 2022 American Association for the Advancement of Science. All rights reserved.",
year = "2022",
month = dec,
day = "23",
doi = "10.1126/science.add1884",
language = "English (US)",
volume = "378",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6626",
}