MOLECULAR MECHANISM FOR NEURAL FROMATION BY BMP

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Presumptive ectoderm gives rise to epidermal or naural tissues and the fate determination is made during gastrulation. Since after the experiments by Spemann and Mangold in 1920's showing that dorsal lip of amphibian can induce secondary body axis with neural tissues including brain and eyes when implanted in ventral side of host embryo, neural tissues are believed to be formed upon the induction triggered by factors emanated from the dorsal lip region of the embryo. However, recent studies on the function of polupeptide growth factors revealed that not epiudemal but neural formation is the ground state. Namely, ectodem is fated to become neural tissue is formed unless it is induced to become epidemis by BMP.Furthemore, it has recently been shown that neural induction takes place because BMP activity is inhibited by its binding proteins such as noggin and chordin.In this study, we have shown that follistatin which was originally known as an activin-binding protein, is able to bind BMP … More Thus follistatin inhibits epidermal inducging activity of BMP thereby induces neural fate. We further confirmed that tyhe interaction between follistatin and BMP and found that the dissociation of the complex is very fast, which makes detection of the interaction between follistatin and BMP and found that the dissociation of the complex is very fast, which makes detection of the interaction by conventional biochemical way difficult. The signal of BMP is mediated through cell surface ser/thr kinase recepotrs and intracellular mediators. To clarify the intyracellular signaling mechanism of BMP,we have screened for signaling moleculeS and target gene of BMP.We first identified a novel MAPKKK TAK1 as a mediater of BMP signal in Xenopus.Because overexpression of a dominant negative (kinase negatuive) TAK1 induced neural fate, TAK1 was suggested to be a mediatoR of BMP signal. We identified a homebox gene msx-1 as an immediate early gene responding to BMP-2 and BMP-4. We further confirmed that msx-1 overexpression leads to the phenotype reminicent to gain-of function of BMP.Our study has clarified a part of BMP signaling in the pathway of neural inhibition. Less