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

11 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Clovis, Y. M., Seo, S. Y., Kwon, J. S., Rhee, J. C., Yeo, S., Lee, J., Lee, S., & Lee, S-K. (Accepted/In press). Chx10 Consolidates V2a Interneuron Identity through Two Distinct Gene Repression Modes. Cell Reports. https://doi.org/10.1016/j.celrep.2016.06.100