@article{ad878450c66f4c429e5b4979bab35db6,
title = "Mir-17-3p Controls Spinal Neural Progenitor Patterning by Regulating Olig2/Irx3 Cross-Repressive Loop",
abstract = "Neural patterning relies on transcriptional cross-repressive interactions that ensure unequivocal assignment of neural progenitor identity to proliferating cells. Progenitors of spinal motor neurons (pMN) and V2 interneurons (p2) are specified by a pair of cross-repressive transcription factors, Olig2 and Irx3. Lineage tracing revealed that many p2 progenitors transiently express the pMN marker Olig2 during spinal cord development. Here we demonstrate that the repression of Olig2 in p2 domain is controlled by mir-17-3p microRNA-mediated silencing of Olig2 mRNA. Mice lacking all microRNAs or just the mir-17~92 cluster manifest a dorsal shift in pMN/p2 boundary and impairment in the production of V2 interneurons. Our findings suggest that microRNA-mediated repression of Olig2 mRNA plays a critical role during the patterning of ventral spinal progenitor domains by shifting the balance of cross-repressive interactions between Olig2 and Irx3 transcription factors.",
author = "Chen, {Jun An} and Huang, {Yuan Ping} and Mazzoni, {Esteban O.} and Tan, {G. Christopher} and Jiri Zavadil and Hynek Wichterle",
note = "Funding Information: Special thanks to Andrea Ventura (Memorial Sloan-Kettering Cancer Center) for kindly providing mir-17∼92 +/− founder mice and conditional mir-17∼92 floxed ES cells and for the discussion of our results. We thank Ben Novitch (UCLA) for sharing Olig2-cre mice, Tom Jessell for reagents and antibodies, and Michael Kyba (University of Minnesota) for providing inducible 2lox-ES cells. We also thank Laskaro Zagoraiou for her help with analysis of V2 interneurons. We are grateful to Asa Abeliovich and Jongpil Kim for sharing reagents for the initial set of pilot studies. We would like to thank Fiona Doetsch for critical reading of the manuscript, discussion, and comments, and Rosalind Bogan for help with manuscript preparation. We would like to acknowledge The NYU Cancer Institute Genomics Facility for expert assistance with microRNA TLDA profiling. E.O.M. was in part supported by Damon Runyon Cancer Research Fund fellowship and G.C.T. was in part funded by NIH training grant (T32HD55165). This research was supported by NIH grants (NS058502 and NS055923). ",
year = "2011",
month = feb,
day = "24",
doi = "10.1016/j.neuron.2011.01.014",
language = "English (US)",
volume = "69",
pages = "721--735",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "4",
}