title: Specific functions for ERK/MAPK signaling during PNS development.
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.
authors.affiliation: University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Newbern
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Shoemaker
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhou
authors.forename: Jian
authors.initials: J
authors.lastname: Zhong
authors.forename: Yaohong
authors.initials: Y
authors.lastname: Wu
authors.forename: Daniel
authors.initials: D
authors.lastname: Bonder
authors.forename: Steven
authors.initials: S
authors.lastname: Hollenback
authors.forename: Giovanni
authors.initials: G
authors.lastname: Coppola
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Geschwind
authors.forename: Gary E
authors.initials: GE
authors.lastname: Landreth
authors.forename: William D
authors.initials: WD
authors.lastname: Snider
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D048052:Mitogen-Activated Protein Kinase 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D048054:Mitogen-Activated Protein Kinase 7 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009046:Motor Neurons / Q000378:metabolism / Q000648:ultrastructure; D009186:Myelin Sheath / Q000648:ultrastructure*; D009432:Neural Crest / Q000254:growth & development*; D009836:Oligodendroglia / Q000378:metabolism* / Q000648:ultrastructure; D017933:Peripheral Nervous System / Q000254:growth & development*; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D048052:Mitogen-Activated Protein Kinase 3; D048054:Mitogen-Activated Protein Kinase 7