Regulation of E- and P-Cadherin Expression Correlated with Melanocyte Migration and Diversification

Abstract

Melanocytes (Mc) and their progenitors melanoblasts (Mb) are derived from the neural crest and migrate along the dorsolateral pathway to colonize the dermis, the epidermis, and finally the hair matrix. To examine the involvement of cadherins in the migration of Mc lineage cells, we combined flow cytometric analysis of dissociated live cells with immunohistochemical staining of tissue sections to quantify the level of cadherin expression on the surface of Mb/Mc. At 11.5 days postcoitum, Mb are in the dermis and are E-cadherin−P-cadherin− (E-cad−P-cad−). During the next 48 h, a 200-fold increase of E-cadherin expression is induced on the surface of Mb prior to their entry into the epidermis, thereby forming a homogeneous E-cadhighP-cad−/low population. The cadherin expression pattern then diversifies, giving rise to three populations, an E-cad−P-cad− dermal population, E-cadhighP-cadlow epidermal population, and E-cad−P-cadmed-high follicular population. In all three populations, the patterns of expression are region-specific, being identical with those of surrounding cells such as keratinocytes and fibroblasts, and are preserved before and after pigmentation. While most of the epidermal Mb/Mc disappear after the neonatal stage in normal mice, forced expression of steel factor in the epidermis of transgenic mice promotes survival of epidermal Mb/Mc, maintaining epidermal-type cadherin expression pattern (E-cadhighP-cadlow) throughout the postnatal life. These findings indicate the involvement of extrinsic cues in coordinating the cadherin expression pattern of Mb/Mc and suggest a role for E- and P-cadherins in guiding Mc progenitors to their final destinations.