Involvement of p21^ras in Xenopus mesoderm induction

Abstract

DURING early vertebrate embryogenesis, mesoderm is specified by a signal emanating from prospective endoderm. This signal can respecify Xenopus prospective ectoderm as mesoderm, and can be mimicked by members of the fibroblast growth factor and transforming growth factor-β families^1,2. In other systems, the p21^c-ras proto-oncogene product has been implicated in signal transduction for various polypeptide growth factors. We report here that a dominant inhibitory ras mutant blocks the mesoderm-inducing activity of fibroblast growth factor and activin, as well as the endogenous inducing activity of prospective endoderm. A constitutively active ras mutant partially mimics these activities. These results indicate that p21^ras may have a central role in the transduction of the mesoderm inductive signal. Basic fibroblast growth factor^3,4 and activin^5–8 have emerged as candidates for endogenous mesoderm-inducing molecules. The character of the mesoderm induced by these two factors is overlapping but distinct when assessed both by histological and molecular criteria^9,10. The signal transduction pathways used during induction by these factors are unknown. We used messenger RNA microinjection of Xenopus eggs to express a dominant inhibitory mutant ras, p21(Asn 17)^Ha-ras, in cells competent to respond to inducing factors to examine the role of p21^ras in this response. This mutant, which has a reduced affinity for GTP relative to GDP¹¹, blocks a variety of mitogenic signals in 3T3 fibroblasts¹² as well as the differentiation of pheochromocytoma cells in response to nerve growth factor¹³.