Specific Functions for ERK/MAPK Signaling during PNS Development

Jason M. Newbern, Xiaoyan Li, Sarah E. Shoemaker, Jiang Zhou, Jian Zhong, Yaohong Wu, Daniel Bonder, Steven Hollenback, Giovanni Coppola, Daniel H. Geschwind, Gary E. Landreth, William D. Snider

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126 Scopus citations

Abstract

We have established functions of the stimulus-dependent MAPKs, ERK1/2 and ERK5, in DRG, motor neuron, and Schwann cell development. Surprisingly, many aspects of early DRG and motor neuron development were found to be ERK1/2 independent, and Erk5 deletion had no obvious effect on embryonic PNS. In contrast, Erk1/2 deletion in developing neural crest resulted in peripheral nerves that were devoid of Schwann cell progenitors, and deletion of Erk1/2 in Schwann cell precursors caused disrupted differentiation and marked hypomyelination of axons. The Schwann cell phenotypes are similar to those reported in neuregulin-1 and ErbB mutant mice, and neuregulin effects could not be elicited in glial precursors lacking Erk1/2. ERK/MAPK regulation of myelination was specific to Schwann cells, as deletion in oligodendrocyte precursors did not impair myelin formation, but reduced precursor proliferation. Our data suggest a tight linkage between developmental functions of ERK/MAPK signaling and biological actions of specific RTK-activating factors.

Original languageEnglish (US)
Pages (from-to)91-105
Number of pages15
JournalNeuron
Volume69
Issue number1
DOIs
StatePublished - Jan 13 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Newbern, J. M., Li, X., Shoemaker, S. E., Zhou, J., Zhong, J., Wu, Y., Bonder, D., Hollenback, S., Coppola, G., Geschwind, D. H., Landreth, G. E., & Snider, W. D. (2011). Specific Functions for ERK/MAPK Signaling during PNS Development. Neuron, 69(1), 91-105. https://doi.org/10.1016/j.neuron.2010.12.003