Retinoid Signaling and Neurogenin2 Function Are Coupled for the Specification of Spinal Motor Neurons through a Chromatin Modifier CBP

Seunghee Lee, Bora Lee, Jae W. Lee, Soo Kyung Lee

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Extracellular signals and cell-intrinsic transcription factors cooperatively instruct generation of diverse neurons. However, little is known about how neural progenitors integrate both cues and orchestrate chromatin changes for neuronal specification. Here, we report that extrinsic signal retinoic acid (RA) and intrinsic transcription factor Neurogenin2 (Ngn2) collaboratively trigger transcriptionally active chromatin in spinal motor neuron genes during development. Retinoic acid receptor (RAR) binds Ngn2 and is thereby recruited to motor neuron genes targeted by Ngn2. RA then facilitates the recruitment of a histone acetyltransferase CBP to the Ngn2/RAR-complex, markedly inducing histone H3/H4-acetylation. Correspondingly, timely inactivation of CBP and its paralog p300 results in profound defects in motor neuron specification and motor axonal projection, accompanied by significantly reduced histone H3-acetylation of the motor neuron enhancer. Our study uncovers the mechanism by which extrinsic RA-signal and intrinsic transcription factor Ngn2 cooperate for cell fate specification through their synergistic activity to trigger transcriptionally active chromatin.

Original languageEnglish (US)
Pages (from-to)641-654
Number of pages14
JournalNeuron
Volume62
Issue number5
DOIs
StatePublished - Jun 11 2009

Keywords

  • DEVBIO
  • MOLNEURO
  • SIGNALING

ASJC Scopus subject areas

  • Neuroscience(all)

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