SCF/c-kit signaling pathway in development.

(A) c-kit⁺ cells present in the BM and spleen of wild-type (control), Steel mutant (Sl/Sl^d), and W mutant (W/W^v) after the induction of hemolytic anemia with PHZ. For cell sorter separation, cells were incubated with c-kit-PE and c-kit⁺ cells sorted by FACS. Sorted cells were then re-analyzed for purity with the cytometer; purity was 95% or greater. (B) Expression of Slug was analyzed by RT-PCR in the purified c-kit⁺ cells of BM and spleen from control, Sl/Sl^d, and W/W^v mice. PCR products were transferred to a nylon membrane and analyzed by hybridization with end-labeled internal oligonucleotide probe specific for theSlug gene (upper panel). β-Actin was used to check cDNA integrity and loading (bottom panel). (C) Model of the function of the SCF/c-kit signaling pathway in development. The SCF/c-kit signaling pathway impairs the development of 3 stem populations: melanoblasts, hematopoietic stem cells, and germ cells. Data presented here indicate that Slug contributes to the functions of SCF/c-kit in melanoblasts and hematopoietic cells, though there are Slug-independent aspects of melanocyte development and hematopoiesis. Identification of the molecular mechanism mediating the mast cell defect is still pending. Within the germ cells, SCF/c-kit function is mediated by Slug (this paper) and PI 3-kinase.35 36 The impairment of Leydig cell development in the absence of Slug could secondarily affect germ cell maturation.