| Co-Investigator(Kenkyū-buntansha) |
CHO Ken W.Y. UNIV.CALFORNIA,IRVINE,ASOC.PROF., アーバイン校, 準教授
HEMMATIーBRIV ロックフェラー大学, 準教授
THOMSEN Gera ニューヨーク州立大学, ストーニーブルック校, 助教授
THOMSEN Gerald H. SUNY,STONYBROOK AST.PROF.
BRIVANLOU Alihemmati ROCKFEELLER UNIV.ASO.PROF.
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| Research Abstract |
In the late 80's, it has been proposed that polypeptide growth factors are playing essential roles in the regulation of early development. Since then extensive studies on the function of growth factors in the paterning of embryo have been carried out by developmental biologists. Studies using Xenopus laevis clarified that growth factors are involved in at least two inductions, cell-to-cell interactions controlling early embryogenesis. They are mesoderm induction and neural induction. During the course of this collaboration program, we have shown that members of TGF-b superfamily activin and Vgl can induce dorsal mesoderm such as notochord and muscle. In contrast another member of the TGF-b family, bone morphogenetic protein (BMP) was shown to induce ventral mesoderm such as blood.
The other induction, neural induction was found to be regulated by BMP.BMP appears to inhibit neural induction of ectoderm by inducing epidermis. We proposed a model that Xenopus ectoderm is fated to become naural tunless the neural fate is inhibited by ventrally located BMP activity. This model further suggests that neural fate is a default state. Recent study identified BMP-binding proteins such as noggin, chordin, and follistatin to be BMP-binding poteins, which is therefore acting as neural inducers.
Finally, we have also identified componets acting in the pathway regulated BMP.They include receptors for acrtivin and BMP,both of which are Ser/Thr kinases, Smad, and a novel MAPKKK,TAKI.We have shown that they also play important roles in early embryogenesis acting down stream of BMP.Particularly, homeobox gene Msx-1 was shown to mimick the action of BMP : over expression of Msx-1 in dorsal blastomeres of Xenopus ventralizes the embryo.
Together, we believe our effort in this international collaboration clarified important part of moleauclr mechanism of growth factor function in the regulation of early development.
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