Studies on the role of growth factors in embryonic inductions

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Growth factors have been implicated in the regulation of early development. Although activin,a member of TGF-beta related growth factor family was discovered as a stimulator of FSH secretion from pituitary cells,it has recently been shown to induce mesodermal tissues from presumptive ectoderm of Xenopus laevis. In order to understand more precisely the molecular mechanism of the mesoderm induction,we have screened a genomic DNA library of Xenopus laevis with rat activin betaALPHA gene as a probe. We have isolated 5 independent genes and one of the genes was found to be encoding a protein closely related to mammalian activin. Interestingly,the rest of the gene contained an amphibian counterpart of mammalian bone morphogenetic proteins, which was purifed based on their ability to induce ectopic bone formation in vivo. Eventually,we isolated cDNAs of Xenopus activin,BMP-2,-4 and -7.Functional analysis has been performed for the growth factor cDNAs by injecting their RNA into early blastomeres early Xenopus embryos to see the effect of overexpression of their gene product. Overexpression of activin in ventral half resulted in duplication of body axis,suggesting that activin play a role in dorsalization. On the other hand,over expression of BMP-4 in dorsal half inhibited the formation of anterior and dorsal structure,suggesting that BMP may be important for ventralization. These results suggest that activin and BMP have distinct role in pattern formation of early embryos.