SPATIAL AND TEMPORAL PATTERNS OF C-KIT-EXPRESSING CELLS IN W-LACZ + AND W-LACZ/W-LACZ MOUSE EMBRYOS/

In the mouse, the Kit receptor and its ligand, the stem cell factor (S CF), are encoded at the W/Kit and Steel loci, respectively. The Kit/SC F transduction pathway is involved in promoting cellular migration, pr oliferation and/or survival of melanoblasts, hematopoietic progenitors and primordial germ cells. Furthermore, a functional Kit/SCF pathway is required for the development of interstitial cells of Cajal (ICC) i n the small intestine. Whereas all c-kif-expressing cells in embryogen esis were not identified, previous studies clearly demonstrated that t he c-kit expression pattern extends well beyond cells known to be affe cted by W mutations. To investigate further Kit function, we specifica lly marked the c-kit-expressing cells and followed their fate during e mbryogenesis. A mutation was introduced by gene targeting at the W/Kit locus in mouse embryonic stem cells. The lacZ reporter gene was inser ted into the first exon of c-kit, thus creating a null allele, called W-lacZ. The lacZ expression reflects normal expression of the c-kit ge ne in W-lacZ/+ embryos. The comparison of the patterns of lacZ-express ing cells between W-lacZ/+ and W-lacZ/W-lacZ embryos allowed us to det ect where and when melanoblasts, primordial germ cells and hematopoiet ic progenitors failed to survive in the absence of Kit. We also observ ed that ICC express c-kit during embryogenesis, ICC are found identica lly in W-lacZ/+ and W-lacZ/W-lacZ embryos. Therefore, ICC do not depen d on Kit expression during embryogenesis. These results indicate that the function of the c-kit gene is only required for the postnatal deve lopment of the ICC. Unexpected sites of c-kit expression were uncovere d in embryos, including endothelial, epithelial and endocrine cells. N one of these cells are dependent on Kit expression for their migration , proliferation and/or survival during embryogenesis. Nevertheless, we assume that the Kit/SCF pathway could be involved in the growth of tr ansformed endothelial, epithelial and endocrine cells.