ACTIVATION OF THE RECEPTOR TYROSINE KINASE KIT IS REQUIRED FOR THE PROLIFERATION OF MELANOBLASTS IN THE MOUSE EMBRYO

The development of neural crest-derived melanocytes, as well as haemat opoietic and germ cells, is affected by mutations of the Kit and Mgf g enes, which lead to dominant spotting (W) or steel (S1) phenotypes. Mg f codes for the ligand of the receptor tyrosine kinase encoded by the Kit locus. Kit(W-v), a point mutation exerting a dominant negative eff ect, causes a substantial reduction in tyrosine kinase activity of the Kit receptor and leads to a characteristic pigmentation phenotype, na mely dilute coat colour and a white ventral and head spot with reduced pigmentation of the feet and tail in the heterozygous animal, as well as slight anaemia. Homozygous animals lack coat pigmentation and are severely anaemic and infertile. Dct is a marker for cells of the melan oblast lineage. In order to study these cells in detail we have genera ted transgenic mouse lines carrying the lacZ reporter under the contro l of the Dct promoter and have used the embryonic expression of the re porter to identify early melanoblasts before they begin to produce pig ment. Our transgenic lines have simplified the study of melanoblasts i n the mouse embryo, and by crossing our mice with Kit(W-v) mutants we have been able to identify the midgestation stages at which melanoblas ts rely critically on Mgf/Kit interactions. We conclude that the survi val of immature melanoblasts depends crucially upon Kit signalling up until E11, and later in development Kit plays a vital role in melanobl ast proliferation. Our data do not describe a dependence upon Kit for melanoblast migration or differentiation. (C) 1997 Academic Press.