Endothelin 3 induces the reversion of melanocytes to glia through a neuralcrest-derived glial-melanscytic progenitor

Functional signaling of endothelin 3 (ET3) and its receptor B (ETRB) has be en shown to be required for the development of neural crest (NC)-derived pi gment cells in mouse, but the precise role of ET3 is not completely underst ood. Using the avian embryo as a model, we previously reported that ET3 pro motes the survival and proliferation of unipotent melanocyte and bipotent g lia-melanocyte precursors in trunk NC cultures. Here we investigated whethe r, at later stages, embryonic pigment cells respond to ET3. Such a possibil ity is supported by the previous finding that, in vivo, avian melanocytes e xpress endothelin receptor B2 (ETRB2) during migration and after their diff erentiation in the skin. We found that in vitro ET3 exerts a dose-dependent stimulation of proliferation and melanogenesis in NC cells that had homed to the epidermis of embryonic quail dorsal skin. Moreover, in clonal cultur es of skin-derived pigment cells, ET3 induces rapid cell divisions of clono genic melanocytes that generate a mixed progeny of melanocytes and cells de void of pigment granules and expressing glial markers in more than 40% of t he colonies. It can therefore be concluded that ET3 is strongly mitogenic t o embryonic pigment cells and able to alter their differentiation program, leading them to recapitulate the glial-melanocyte bipotentiality of their N C ancestors.