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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

103 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

Funding

We thank the Mental Retardation Developmental Disabilities Research Center Gene Manipulation Core Facility of Children's Hospital Boston for their help with making the knockin mice. We thank Dr. Gordon N. Gill for providing the anti-NLI antibody, Dr. Charles D. Stiles for the anti-Olig2 antibody, and Dr. William D. Snider and Dr. David L. Turner for GSK3 RNAi constructs. We thank members of the Greenberg laboratory for critically reading the manuscript. Y.C.M. was supported by fellowships from the American Cancer Society and the William Randolph Hearst Foundation. H.-Y.H.H. is the Marion Abbe Fellow supported by the Damon Runyon Cancer Research Foundation (DRG-1896-05). This research was supported by National Institute of Neurological Disorders and Stroke (NINDS) grant R37NS037116 (S.L.P.), grant PO1NS047572 (M.E.G.), and a Mental Retardation Developmental Disabilities Research Center grant HD18655 (M.E.G.). M.E.G. acknowledges the generous support of the F.M. Kirby Foundation to the Children's Hospital F.M. Kirby Neurobiology Center.

Keywords

  • DEVBIO
  • MOLNEURO

ASJC Scopus subject areas

  • General Neuroscience

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