Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis

The three mammalian Raf serine/threonine protein kinases mediate the transd uction of proliferative and differentiative signals from cell surface recep tors to the nucleus. In vertebrates, Raf signaling has been implicated in t he progression of mouse embryos through the two-cell stage and in the induc tion of posterior mesoderm. However, mouse embryos mutant for each of the R af genes exhibit no developmental defects before mid-gestation. Here we des cribe the phenotype of mouse mutants with different combinations of mutant Craf-1 and Braf alleles. Our results show that Raf signaling is indeed indi spensable for normal development beyond the blastocyst stage. However, due to a significant redundancy between Craf-1 and Braf, either gene is suffici ent for normal development until mid-gestation. The molecular and developme ntal mechanisms for this redundancy were investigated by monitoring the exp ression of Raf genes throughout embryogenesis and by biochemical studies in mutant cell lines. (C) 2000 Elsevier Science Ireland Ltd. All rights reser ved.