Transcriptional repression coordinates the temporal switch from motor to serotonergic neurogenesis

John Jacob, Anna L. Ferri, Christopher Milton, Fabrice Prin, Patrick Pla, Wei Lin, Anthony Gavalas, Siew Lan Ang, James Briscoe

Research output: Contribution to journalArticlepeer-review

Abstract

In many regions of the developing CNS, distinct cell types are born at different times. The means by which discrete and stereotyped temporal switches in cellular identities are acquired remains poorly understood. To address this, we have examined how visceral motor neurons (VMNs) and serotonergic neurons, two neuronal subtypes, are sequentially generated from a common progenitor pool in the vertebrate hindbrain. We found that the forkhead transcription factor Foxa2, acting in progenitors, is essential for the transition from VMN to serotonergic neurogenesis. Loss-of-function and gain-of-function experiments indicated that Foxa2 activates the switch through a temporal cross-repressive interaction with paired-like homeobox 2b (Phox2b), the VMN progenitor determinant. This mechanism bears a marked resemblance to the cross-repression between neighboring domains of transcription factors that establish discrete progenitor identities along the spatial axes. Moreover, the subsequent differentiation of central serotonergic neurons required both the suppression of VMN neurogenesis and the induction of downstream intrinsic determinants of serotonergic identity by Foxa2.

Original languageEnglish
Pages (from-to)1433-1439
Number of pages7
JournalNature Neuroscience
Volume10
Issue number11
DOIs
Publication statusPublished - Nov 2007

ASJC Scopus subject areas

  • Neuroscience(all)

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