Specific Functions for ERK/MAPK Signaling during PNS Development

被引:180
作者
Newbern, Jason M. [1 ]
Li, Xiaoyan [1 ]
Shoemaker, Sarah E. [1 ]
Zhou, Jiang [1 ]
Zhong, Jian [4 ]
Wu, Yaohong [1 ]
Bonder, Daniel [1 ]
Hollenback, Steven [1 ]
Coppola, Giovanni [3 ]
Geschwind, Daniel H. [3 ]
Landreth, Gary E. [2 ]
Sniderl, William D. [1 ]
机构
[1] Univ N Carolina, UNC Neurosci Ctr, Chapel Hill, NC 27599 USA
[2] Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Program Neurogenet, Los Angeles, CA 90024 USA
[4] Cornell Univ, Weill Med Coll, Burke Med Res Inst, Dept Neurol & Neurosci, White Plains, NY 10605 USA
关键词
PERIPHERAL NERVOUS-SYSTEM; ACTIVATED PROTEIN-KINASE; SCHWANN-CELL DEVELOPMENT; SENSORY AXON GROWTH; IN-VIVO; NEURONAL SURVIVAL; REGULATED KINASE; GLIAL-CELLS; MYELINATION; DIFFERENTIATION;
D O I
10.1016/j.neuron.2010.12.003
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:91 / 105
页数:15
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