The murine W/c-kit and Steel loci and the control of hematopoiesis.
The experiments summarized here indicate that germ-line mutations in either the c-kit receptor tyrosine kinase (W mutants) or its ligand (Sl) lead to profound and pleiotropic developmental defects, including abnormalities within the hematopoietic system. These observations parallel findings in other developmental systems, notably the fruit fly Drosophila, that receptor tyrosine kinases play key roles in the determination of cell fate and the elaboration of developmental programs. Thus, it appears that the processes of hematopoiesis, melanogenesis, and gametogenesis in mammals involve a similar strategy to that used in other species for transmitting and receiving positional cues during development. Finally, it is interesting to note that what began as an attempt to understand the molecular basis of coat color mutations in the mouse has led to the identification of a key cell-signalling pathway in the development of at least three cell lineages in mammals. Further analysis of the W/Sl pathway should provide a more complete understanding of the early events in hematopoiesis, and may also lead to novel therapeutic applications involving the protein product of the Sl locus.
Bernstein
A
A
Division of Molecular and Developmental Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canda.
Forrester
L
L
Reith
A D
AD
Dubreuil
P
P
Rottapel
R
R
D000818:Animals; D002478:Cells, Cultured; D006410:Hematopoiesis / Q000235:genetics*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit; D011519:Proto-Oncogenes
D011518:Proto-Oncogene Proteins; D019009:Proto-Oncogene Proteins c-kit