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 language | English (US) |
|---|---|
| Pages (from-to) | 721-735 |
| Number of pages | 15 |
| Journal | Neuron |
| Volume | 69 |
| Issue number | 4 |
| DOIs | |
| State | Published - Feb 24 2011 |
Fingerprint
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Mir-17-3p Controls Spinal Neural Progenitor Patterning by Regulating Olig2/Irx3 Cross-Repressive Loop. / Chen, Jun An; Huang, Yuan Ping; Mazzoni, Esteban O.; Tan, G. Christopher; Zavadil, Jiri; Wichterle, Hynek.
In: Neuron, Vol. 69, No. 4, 24.02.2011, p. 721-735.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Mir-17-3p Controls Spinal Neural Progenitor Patterning by Regulating Olig2/Irx3 Cross-Repressive Loop
AU - Chen, Jun An
AU - Huang, Yuan Ping
AU - Mazzoni, Esteban O.
AU - Tan, G. Christopher
AU - Zavadil, Jiri
AU - Wichterle, Hynek
PY - 2011/2/24
Y1 - 2011/2/24
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79951691238&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79951691238&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2011.01.014
DO - 10.1016/j.neuron.2011.01.014
M3 - Article
VL - 69
SP - 721
EP - 735
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -