TY - JOUR
T1 - Specific Functions for ERK/MAPK Signaling during PNS Development
AU - Newbern, Jason M.
AU - Li, Xiaoyan
AU - Shoemaker, Sarah E.
AU - Zhou, Jiang
AU - Zhong, Jian
AU - Wu, Yaohong
AU - Bonder, Daniel
AU - Hollenback, Steven
AU - Coppola, Giovanni
AU - Geschwind, Daniel H.
AU - Landreth, Gary E.
AU - Snider, William D.
N1 - Funding Information:
We are extremely grateful to D. Meijer, T. Jessell, and J. Charron for providing transgenic mice; Ben Novitch, Barbara Han, and Monica Mendelsohn for the generation of the Olig2:Cre line in the laboratory of T. Jessell; T. Müller and C. Birchmeier for the generous gift of the BFABP antibody and helpful advice; E. Anton and J. Weimer for kindly providing antibodies and guidance; Dr. Louis Reichardt for kindly providing the TrkA antibody; and A. McKell and L. Goins for assistance with mouse breeding and genotyping. This work is supported by NIH grant NS031768 to W.D.S.; NSF grant IBN97–23147 to G.E.L.; and a NRSA award F32NS061591 to J.M.N. Generation of mice and imaging were supported by Cores 3 and 5, respectively, of NINDS Center Grant P30 NS04892.
PY - 2011/1/13
Y1 - 2011/1/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=78650939557&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2010.12.003
DO - 10.1016/j.neuron.2010.12.003
M3 - Article
C2 - 21220101
AN - SCOPUS:78650939557
SN - 0896-6273
VL - 69
SP - 91
EP - 105
JO - Neuron
JF - Neuron
IS - 1
ER -