Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes

Yoanne M. Clovis, So Yeon Seo, Ji sun Kwon, Jennifer C. Rhee, Sujeong Yeo, Jae Lee, Seunghee Lee, Soo-Kyung Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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. Clovis et al. describe the mechanism through which spinal V2a interneurons are specified. They find that the best-known marker for V2a interneurons, Chx10, is the major determinant of V2a fate specification. Chx10 upregulates the expression of V2a interneuron genes while suppressing the expression of non-V2a interneuron and motor neuron genes.

Original languageEnglish (US)
JournalCell Reports
DOIs
StateAccepted/In press - Feb 4 2016

Fingerprint

Motor Neurons
Interneurons
Neurons
Genes
Developmental Genes
Efferent Pathways
Specifications
Regulator Genes
Transcription
Cell Differentiation
Up-Regulation

Keywords

  • Chx10
  • Development
  • Lhx3
  • Motor neurons
  • Sox14
  • Spinal cord
  • Transcription factor
  • V2a interneurons
  • Vsx2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes. / Clovis, Yoanne M.; Seo, So Yeon; Kwon, Ji sun; Rhee, Jennifer C.; Yeo, Sujeong; Lee, Jae; Lee, Seunghee; Lee, Soo-Kyung.

In: Cell Reports, 04.02.2016.

Research output: Contribution to journalArticle

Clovis, Yoanne M. ; Seo, So Yeon ; Kwon, Ji sun ; Rhee, Jennifer C. ; Yeo, Sujeong ; Lee, Jae ; Lee, Seunghee ; Lee, Soo-Kyung. / Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes. In: Cell Reports. 2016.
@article{9c1fe967fb644c69bc7498fb1df7ae60,
title = "Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes",
abstract = "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. Clovis et al. describe the mechanism through which spinal V2a interneurons are specified. They find that the best-known marker for V2a interneurons, Chx10, is the major determinant of V2a fate specification. Chx10 upregulates the expression of V2a interneuron genes while suppressing the expression of non-V2a interneuron and motor neuron genes.",
keywords = "Chx10, Development, Lhx3, Motor neurons, Sox14, Spinal cord, Transcription factor, V2a interneurons, Vsx2",
author = "Clovis, {Yoanne M.} and Seo, {So Yeon} and Kwon, {Ji sun} and Rhee, {Jennifer C.} and Sujeong Yeo and Jae Lee and Seunghee Lee and Soo-Kyung Lee",
year = "2016",
month = "2",
day = "4",
doi = "10.1016/j.celrep.2016.06.100",
language = "English (US)",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",

}

TY - JOUR

T1 - Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes

AU - Clovis, Yoanne M.

AU - Seo, So Yeon

AU - Kwon, Ji sun

AU - Rhee, Jennifer C.

AU - Yeo, Sujeong

AU - Lee, Jae

AU - Lee, Seunghee

AU - Lee, Soo-Kyung

PY - 2016/2/4

Y1 - 2016/2/4

N2 - 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. Clovis et al. describe the mechanism through which spinal V2a interneurons are specified. They find that the best-known marker for V2a interneurons, Chx10, is the major determinant of V2a fate specification. Chx10 upregulates the expression of V2a interneuron genes while suppressing the expression of non-V2a interneuron and motor neuron genes.

AB - 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. Clovis et al. describe the mechanism through which spinal V2a interneurons are specified. They find that the best-known marker for V2a interneurons, Chx10, is the major determinant of V2a fate specification. Chx10 upregulates the expression of V2a interneuron genes while suppressing the expression of non-V2a interneuron and motor neuron genes.

KW - Chx10

KW - Development

KW - Lhx3

KW - Motor neurons

KW - Sox14

KW - Spinal cord

KW - Transcription factor

KW - V2a interneurons

KW - Vsx2

UR - http://www.scopus.com/inward/record.url?scp=84979730133&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979730133&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2016.06.100

DO - 10.1016/j.celrep.2016.06.100

M3 - Article

C2 - 27477290

AN - SCOPUS:84979730133

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

ER -