The EGFR is required for proper innervation to the skin.
EGFR family members are essential for proper peripheral nervous system development. A role for EGFR itself in peripheral nervous system development in vivo, however, has not been reported. We investigated whether EGFR is required for cutaneous innervation using Egfr null and skin-targeted Egfr mutant mice. Neuronal markers; including PGP9.5, GAP-43, acetylated tubulin, and neurofilaments; revealed that Egfr null dorsal skin was hyperinnervated with a disorganized pattern of innervation. In addition, receptor subtypes such as lanceolate endings were disorganized and immature. To determine whether the hyperinnervation phenotype resulted from a target-derived effect of loss of EGFR, mice lacking EGFR expression in the cutaneous epithelium were examined. These mice retained other aspects of the cutaneous Egfr null phenotype but exhibited normal innervation. The sensory deficits in Egfr null dorsal skin were not associated with any abnormality in the morphology or density of dorsal root ganglion (DRG) neurons or Schwann cells. However, explant and dissociated cell cultures of DRG revealed more extensive branching in Egfr null cultures. These data demonstrate that EGFR is required for proper cutaneous innervation during development and suggest that it limits axonal outgrowth and branching in a DRG-autonomous manner.
Maklad
Adel
A
Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska 68178, USA.
Nicolai
Jodi R
JR
Bichsel
Kyle J
KJ
Evenson
Jackie E
JE
Lee
Tang-Cheng
TC
Threadgill
David W
DW
Hansen
Laura A
LA
D000818:Animals; D066246:ErbB Receptors / Q000378:metabolism* / Q000502:physiology; D019922:GAP-43 Protein / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D008954:Models, Biological; D009154:Mutation; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism; D012867:Skin / Q000294:innervation*; D014404:Tubulin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
D019922:GAP-43 Protein; D014404:Tubulin; D066246:ErbB Receptors; D043222:Ubiquitin Thiolesterase; C496976:Uchl1 protein, mouse