Regulation of Motor Neuron Specification by Phosphorylation of Neurogenin 2

Yong Chao Ma, Mi Ryoung Song, Jin P. Park, Hsin-Yi Henry Ho, Linda Hu, Martin V. Kurtev, Janine Zieg, Qiufu Ma, Samuel L. Pfaff, Michael E. Greenberg

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

The mechanisms by which proneural basic helix-loop-helix (bHLH) factors control neurogenesis have been characterized, but it is not known how they specify neuronal cell-type identity. Here, we provide evidence that two conserved serine residues on the bHLH factor neurogenin 2 (Ngn2), S231 and S234, are phosphorylated during motor neuron differentiation. In knockin mice in which S231 and S234 of Ngn2 were mutated to alanines, neurogenesis occurs normally, but motor neuron specification is impaired. The phosphorylation of Ngn2 at S231 and S234 facilitates the interaction of Ngn2 with LIM homeodomain transcription factors to specify motor neuron identity. The phosphorylation-dependent cooperativity between Ngn2 and homeodomain transcription factors may be a general mechanism by which the activities of bHLH and homeodomain proteins are temporally and spatially integrated to generate the wide diversity of cell types that are a hallmark of the nervous system.

Original languageEnglish (US)
Pages (from-to)65-77
Number of pages13
JournalNeuron
Volume58
Issue number1
DOIs
StatePublished - Apr 10 2008
Externally publishedYes

Keywords

  • DEVBIO
  • MOLNEURO

ASJC Scopus subject areas

  • Neuroscience(all)

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    Ma, Y. C., Song, M. R., Park, J. P., Ho, H-Y. H., Hu, L., Kurtev, M. V., Zieg, J., Ma, Q., Pfaff, S. L., & Greenberg, M. E. (2008). Regulation of Motor Neuron Specification by Phosphorylation of Neurogenin 2. Neuron, 58(1), 65-77. https://doi.org/10.1016/j.neuron.2008.01.037