ENDOTHELIN-3 SELECTIVELY PROMOTES SURVIVAL AND PROLIFERATION OF NEURAL CREST-DERIVED GLIAL AND MELANOCYTIC PRECURSORS IN-VITRO

Genetic data in the mouse have shown that endothelin 3 (En) and its re ceptor B (ETRB) are essential for the development of two neural crest (NC) derivatives, the melanocytes and the enteric nervous system. We r eport here the effects of En in vitro on the differentiation of quail trunk NC cells (NCC) in mass and clonal cultures. Treatment with ET3 i s highly mitogenic to the undifferentiated NCC population, which leads to expansion of the population of cells in the melanocytic, and to a lesser extent, the glial lineages. The effect of ET3 on these two NC d erivatives was confirmed by the quantitative analysis of clones derive d from individual NCC subjected to ET3: we found a large increase in t he survival and proliferation of unipotent and bipotent precursors for glial cells and melanocytes, with no significant effect on multipoten t cells generating neurons. ET3 first stimulates expression of both ET RB and ETRB2 by cultured NCC. Then, under prolonged exposure to ET3, E TRB expression decreases and switches toward an ETRB2-positive melanog enic cell population. We therefore propose that the present in vitro e xperiments (long-lasting exposure to a high concentration of ET3) mimi c the environment encountered by NCC in vivo when they migrate to the skin under the ectoderm that expresses ET3.