1. ¹Department of Biomedical Sciences, Creighton University School of Medicine, Omaha, Nebraska, USA
2. ²Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA

Correspondence: Dr Laura A. Hansen, Department of Biomedical Sciences, Creighton University School of Medicine, 2500 California Plaza, Omaha, Nebraska 68178 USA. E-mail: LHansen@creighton.edu

³Current Address: Department of Anatomy, University of Mississippi Medical Center, Jackson, Mississippi USA.

Received 24 March 2008; Revised 26 June 2008; Accepted 28 July 2008; Published online 2 October 2008.

Abstract

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.

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