Mitogen-activated protein kinase and neural specification in Xenopus

We have investigated the activity and function of mitogen-activated protein kinase (MAPK) during neural specification in Xenopus, Ectodermal MAPK acti vity increased between late blastula and midgastrula stages. At midgastrula , MAPK activity in both newly induced neural ectoderm and ectoderm overexpr essing the anterior neural inducer noggin was 5-fold higher than in uninduc ed ectoderm. Overexpression of MAPK phosphatase-1 (MKP-1) in ectoderm inhib ited MAPK activity and prevented neurectoderm-specific gene expression when the ectoderm aas recombined with dorsal mesoderm or treated with fibroblas t growth factor (FGF). Neurectoderm-specific gene expression was observed, however, in ectoderm overexpressing both noggin and MKP-1, To evaluate the role of MAPK in posterior regionalization, ectodermal isolates were treated with increasing concentrations of FGF and assayed for MAPK activity and ne urectoderm-specific gene expression. Although induction of posterior neural ectoderm by FGF was accompanied by an elevation of MAPK activity, relative MAPK activity associated with posterior neural fate was no higher than tha t of ectoderm specified to adopt an anterior neural fate. Thus, increasingl y posterior neural fates are not correlated with quantitative increases in MAPK activity. Because MAPK has been shown to do,vn-regulate Smad1, MAPK ma y disrupt bone morphogenetic protein 4 (BMP-4) signaling during neural spec ification. Our results suggest that MAPK plays an essential role in the est ablishment of neural fate in vivo.