Evidence for critical period in development of cutaneous innervation: A study in nude mice

Abstract

Cutaneous sensory structures are important sources for guidance cues and neurotrophic support for the sensory nerves innervating them. Spontaneous mutation of the hair follicles in the skin of nude mice provides an excellent model to test the role played by sensory structures in the development of their sensory innervation. The innervation of the skin in normal and nude mice was compared using several pan neuronal markers and keratin 14 antibodies. The pattern of innervation of the skin was disrupted in nude mice; the normal arrangement of three horizontal nerve plexuses was lost and replaced by random nerve fibers. Also, the density of sensory innervation in nude skin was decreased compared to normal skin. The rudimentary follicles in nude skin did not carry lanceolate endings in the isthmus region or Merkel endings in the rete ridge. To determine if a normal target can reverse these innervation errors, normal skin was grafted onto the dorsal interscapular region of nude skin. Analysis of the innervation pattern in grafted skin revealed that the abnormal pattern persisted. We conclude that hair follicles are required for patterning cutaneous sensory nerves and that the innervation defects cannot be reversed upon exposure to a normal target later in development. The latter finding suggests that a critical window exists for correct pattern formation in the cutaneous sensory nerves.