Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes
Autor: | Jennifer Chiyeon Rhee, Soo Kyung Lee, Seung-Hee Lee, Yoanne M. Clovis, Sujeong Yeo, So Yeon Seo, Jae Woon Lee, Ji Sun Kwon |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Transcriptional Activation Cell type Sox14 SOX14 Interneuron Cellular differentiation Chx10 LIM-Homeodomain Proteins Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Interneurons Lhx3 medicine Animals Vsx2 lcsh:QH301-705.5 development Transcription factor transcription factor Genetics Homeodomain Proteins Motor Neurons Gene Expression Regulation Developmental Cell Differentiation Cell biology 030104 developmental biology medicine.anatomical_structure lcsh:Biology (General) Spinal Cord Transcription preinitiation complex Homeobox LHX3 Chickens 030217 neurology & neurosurgery V2a interneurons Transcription Factors |
Zdroj: | Cell Rep CELL REPORTS(16): 6 Cell Reports, Vol 16, Iss 6, Pp 1642-1652 (2016) |
ISSN: | 2211-1247 |
Popis: | SummaryDuring 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. |
Databáze: | OpenAIRE |
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