Mir-17-3p Controls Spinal Neural Progenitor Patterning by Regulating Olig2/Irx3 Cross-Repressive Loop

Jun An Chen, Yuan Ping Huang, Esteban O. Mazzoni, G. Christopher Tan, Jiri Zavadil, Hynek Wichterle

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)721-735
Number of pages15
JournalNeuron
Volume69
Issue number4
DOIs
StatePublished - Feb 24 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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