The present research proposal continues a series of studies on the differentiation of cutaneous sensory innervation during normal development and compares this process with that of regeneration of sensory receptors. Our baseline studies have used monkey embryos and we now have assumed a complete series of embryos from the first through the third trimester of gestation. Our proposed studies include and analysis of the development of sensory innervation of glabrous and hairy skin of the lip to compare with previous studies in other sites. We will compare the sequence of development in monkey with more limited human autopsy material and a series of opossum postnatal pups, the only non-primate animal with papillary ridges in palmar and plantar glabrous skin. We will compare the sequence of maturation of Merkel, Ruffini, Meissner, lanceolate and intraepidermal and dermal free nerve endings in glabrous as compared to hairy skin. Our completed baseline studies on the development of sensory innervation in hairy and glabrous monkey skin suggested a tight linkage between cutaneous and neural development, and prompted pilot studies on chick embryos and opossum pups following selective lesions of the neural tube. We propose to use the opossum, Monodelphis domesticus, as our experimental model in which we will analyze the sequential changes of cutaneous innervation following nerve transection and nerve crush in intact animals and in animals following partial abalation of the spinal cord. Altered cutaneous development, hyperplasia of residual dorsal root ganglia, and the expansion of the dermatotopic map following partial neuralectomy will be compared in Monodelphis to previous studies on chicken embryos. We will continue to analyze specimens of human skin following nerve transection and crush to better understand the residual sensibility following partial deafferentiation.
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