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 haematopoietic and germ cells, is affected by mutations of the Kit and Mgf genes, which lead to dominant spotting (W) or steel (Sl) phenotypes. Mgf codes for the ligand of the receptor tyrosine kinase encoded by the Kit locus. KitW-v, a point mutation exerting a dominant negative effect, causes a substantial reduction in tyrosine kinase activity of the Kit receptor and leads to a characteristic pigmentation phenotype, namely 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 melanoblast lineage. In order to study these cells in detail we have generated transgenic mouse lines carrying the lacZ reporter under the control of the Dct promoter and have used the embryonic expression of the reporter to identify early melanoblasts before they begin to produce pigment. Our transgenic lines have simplified the study of melanoblasts in the mouse embryo, and by crossing our mice with KitW-v mutants we have been able to identify the midgestation stages at which melanoblasts rely critically on Mgf/Kit interactions. We conclude that the survival of immature melanoblasts depends crucially upon Kit signalling up until E11, and later in development Kit plays a vital role in melanoblast proliferation. Our data do not describe a dependence upon Kit for melanoblast migration or differentiation.
Mackenzie
M A
MA
MRC Human Genetics Unit, Western General Hospital, Edinburgh, EH4 2XU, United Kingdom.
Jordan
S A
SA
Budd
P S
PS
Jackson
I J
IJ
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D003433:Crosses, Genetic; D017931:DNA Primers / Q000235:genetics; D004789:Enzyme Activation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D007763:Lac Operon; D008297:Male; D008544:Melanocytes / Q000166:cytology* / Q000201:enzymology*; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D010859:Pigmentation Disorders / Q000196:embryology / Q000235:genetics; D017354:Point Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics; D019089:Stem Cell Factor / Q000235:genetics
D017931:DNA Primers; D005819:Genetic Markers; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit