Regulation of E- and P-cadherin expression correlated with melanocyte migration and diversification

Melanocytes (Mc) and their progenitors melanoblasts (Mb) are derived from t he neural crest and migrate along the dorsolateral pathway to colonize the dermis, the epidermis, and finally the hair matrix. To examine the involvem ent of cadherins in the migration of Me lineage cells, we combined now cyto metric analysis of dissociated live cells with immunohistochemical staining of tissue sections to quantify the level of cadherin expression on the sur face of Mb/Mc. At 11.5 days postcoitum, Mb are in the dermis and are E-cadh erin(-)P-cadherin(-) (E-cad(-)P-cad(-)). During the next 48 h, a 200-fold i ncrease of E-cadherin expression is induced on the surface of Mb prior to t heir entry into the epidermis, thereby forming a homogeneous E-cad(high)P-c ad(-/low) population. The cadherin expression pattern then diversifies, giv ing rise to three populations, an E-cad(-)P-cad(-) dermal population, E-cad (high)P-cad(low) epidermal population, and E-cad(-)P-Cad(med-high) follicul ar population. In all three populations, the patterns of expression are reg ion-specific, being identical with those of surrounding cells such as kerat inocytes and fibroblasts, and are preserved before and after pigmentation. While most of the epidermal Mb/Mc disappear after the neonatal stage in nor mal mice, forced expression of steel factor in the epidermis of transgenic mice promotes survival of epidermal Mb/Mc, maintaining epidermal-type cadhe rin expression pattern (E-Cad(high)P-Cad(low)) throughout the postnatal lif e. These findings indicate the involvement of extrinsic cues in coordinatin g the cadherin expression pattern of Mb/Mc and suggest a role for E- and P- cadherins in guiding Me progenitors to their final destinations. (C) 1999 A cademic Press.