Regulation of MAP kinase by the BMP-4/TAK1 pathway in Xenopus ectoderm

Bone morphogenetic protein-4 (BMP-4) induces epidermis and represses neural fate in Xenopus ectoderm. Our previous findings implicate p42 Erk MAP kina se (MAPK) in the response to neural induction. We have examined the effects of BMP-4 on MAPK activity in gastrula ectoderm. Expression of a dominant n egative BMP-4 receptor resulted in a 4.5-fold elevation in MAPK activity in midgastrula ectoderm. MAPK activity was reduced in ectoderm expressing a c onstitutively active BMP-4 receptor, or ectoderm treated with BMP-4 protein in the presence or absence of cycloheximide. Overexpression of TAK1 led to a reduction in MAPK activity in early gastrula ectoderm. The inhibitory ef fects of TAK1 could be reversed by 1 muM SB 203580, a p38 inhibitor. Treatm ent of isolated ectoderm with SB 203580 led to expression of otx2, NCAM, an d noggin. Western blot analyses indicated that the BMP-4 pathway does not a ctivate JNKs in ectoderm. Our findings indicate that BMP-4 inhibits ectoder mal MAPK activity through a TAK1/p38-type pathway. MAPK has been shown to i nactivate Smad1. Thus, our results suggest that BMP-4 and MAPK pathways are mutually antagonistic in Xenopus ectoderm, and that interactions between t hese pathways may govern the choice between epidermal and neural fate. (C) 2001 Academic Press.