EFFECTS OF THE STEEL GENE-PRODUCT ON MOUSE PRIMORDIAL GERM-CELLS IN CULTURE

MUTATIONS at the steel (sl) and dominant white spotting (W) loci in the mouse affect primordial germ cells (PGC), melanoblasts and haemopoietic stem cells 1. The W gene encodes a cell-surface receptor of the tyrosine kinase family 2,3, the proto-oncogene c-kit. In situ analysis has shown c-kit messenger RNA expression in PGC in the early genital ridges 4. The Sl gene encodes the ligand for this receptor, a peptide growth factor, called here stem cell factor (SCF) 5-7. SCF mRNA is expressed in many regions of the early mouse embryo, including the areas of migration of these cell types 8. It is important now to identify the role of the Sl-W interaction in the development of these migratory embryonic stem cell populations. Using an in vitro assay system 9, we show that SCF increases both the overall numbers and colony sizes of migratory PGC isolated from wild-type mouse embryos, and cultured on irradiated feeder layers of STO cells (a mouse embryonic fibroblast line). In the absence of feeder cells, SCF causes a large increase in the initial survival and apparent motility of PGC in culture. But labelling with bromodeoxyuridine shows that SCF is not, by itself, a mitogen for PGC. SCF does not exert a chemotropic effect on PGC in in vitro assays. These results suggest that SCF in vivo is an essential requirement for PGC survival. This demonstrates the control of the early germ-line population by a specific trophic factor.