Role of fibroblast growth factor during early midbrain development in Xenopus

Genes encoding fibroblast growth factors (FGFs) are expressed in early Xeno pus neurulae in the prospective midbrain-hindbrain boundary (MHB) region of the neural plate. These expression domains overlap those of XWnt-1 and XEn -2, raising the question of the role of FGF signalling in the regulation of these genes, and more generally about the function of FGF during Xenopus m idbrain development. We report that explants from the prospective MHB graft ed into the anterior neural plate in midneurula stage embryos induce XWnt-1 expression and, at a lower frequency, XEn-2 expression in the vicinity of the graft. Such a process is likely to involve FGF signalling. Implantation of FGF4- or FGF8-soaked beads in the prospective forebrain at neurula and tailbud stages causes the up-regulation of XWnt-1 and XEn-2 in the dorsal a nd lateral region of the anterior midbrain. This effect is not relayed by e ndogenous FGF genes since exogenous FGFs inhibit the expression of endogeno us XFGF3 or XFGF8. However, consequences of grafting MHB or implanting FGF4 or FGF8 beads on tadpole brain development are different. MHB grafts induc e ectopic mesencephalic structures, strongly suggesting that a region homol ogous to the isthmic organizer of amniotes is specified as early as the mid neurula stage. In contrast, exogenous FGFs do not cause the formation of ec topic mesencephalic structures but an overgrowth of mesencephalon and dienc ephalon. We propose that FGF signals from the prospective MHB play a crucia l role in the spatial regulation of XWnt-1 and XEn-2 expression in the post erior midbrain, but that the full organizing activity of the MHB involves o ther factors in combination with FGF. (C) 1998 Elsevier Science Ireland Ltd . All rights reserved.