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

doi:10.1016/j.neuron.2008.01.037

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

Pediatrics

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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 language	English (US)
Pages (from-to)	65-77
Number of pages	13
Journal	Neuron
Volume	58
Issue number	1
DOIs	https://doi.org/10.1016/j.neuron.2008.01.037
State	Published - 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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10.1016/j.neuron.2008.01.037

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title = "Regulation of Motor Neuron Specification by Phosphorylation of Neurogenin 2",

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.",

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

note = "Funding Information: 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. ",

year = "2008",

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doi = "10.1016/j.neuron.2008.01.037",

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AU - Ma, Yong Chao

AU - Song, Mi Ryoung

AU - Park, Jin P.

AU - Henry Ho, Hsin Yi

AU - Hu, Linda

AU - Kurtev, Martin V.

AU - Zieg, Janine

AU - Ma, Qiufu

AU - Pfaff, Samuel L.

AU - Greenberg, Michael E.

N1 - Funding Information: 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.

PY - 2008/4/10

Y1 - 2008/4/10

N2 - 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.

AB - 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.

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JO - Neuron

JF - Neuron

IS - 1

ER -

Regulation of Motor Neuron Specification by Phosphorylation of Neurogenin 2

Abstract

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Keywords

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