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Publication : Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes.

First Author  Clovis YM Year  2016
Journal  Cell Rep Volume  16
Issue  6 Pages  1642-1652
PubMed ID  27477290 Mgi Jnum  J:238975
Mgi Id  MGI:5824643 Doi  10.1016/j.celrep.2016.06.100
Citation  Clovis YM, et al. (2016) Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes. Cell Rep 16(6):1642-52
abstractText  During development, two cell types born from closely related progenitor pools often express identical transcriptional regulators despite their completely distinct characteristics. This phenomenon implies the need for a mechanism that operates to segregate the identities of the two cell types throughout differentiation after initial fate commitment. To understand this mechanism, we investigated the fate specification of spinal V2a interneurons, which share important developmental genes with motor neurons (MNs). We demonstrate that the paired homeodomain factor Chx10 functions as a critical determinant for V2a fate and is required to consolidate V2a identity in postmitotic neurons. Chx10 actively promotes V2a fate, downstream of the LIM-homeodomain factor Lhx3, while concomitantly suppressing the MN developmental program by preventing the MN-specific transcription complex from binding and activating MN genes. This dual activity enables Chx10 to effectively separate the V2a and MN pathways. Our study uncovers a widely applicable gene regulatory principle for segregating related cell fates.
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