BONE MORPHOGENETIC PROTEIN-4 (BMP-4) ACTS DURING GASTRULA STAGES TO CAUSE VENTRALIZATION OF XENOPUS EMBRYOS

Injection of RNA encoding BMP-4 into the early Xenopus embryo suppress es formation of dorsal and anterior cell types. To understand this phe nomenon, it is necessary to know the stage at which BMP-4 acts, In thi s paper, we present three lines of evidence showing that BMP-4 misexpr ession has no effect on the initial steps of mesoderm induction, eithe r dorsal or ventral, but instead causes ventralization during gastrula tion. Firstly, activation of organizer-specific genes such as goosecoi d, Xnot, pintallavis and noggin occurs normally in embryos injected wi th BMP-4 RNA, but transcript levels are then rapidly down-regulated as gastrulation proceeds, Similarly, BMP-4 does not affect the initial a ctivation of goosecoid by activin in animal caps, but expression then declines precipitously, Secondly, embryos made ventral by injection wi th BMP-4 RNA cannot be rescued by grafts of Spemann's organizer at gas trula stages, Such embryos therefore differ from those made ventral by UV-irradiation, where the defect occurs early and rescue can be effec ted by the organizer, Finally, the dorsalizing effects of the organize r, and of the candidate dorsalizing signal noggin, both of which exert their effects during gastrulation, can he counteracted by BMP-4. Toge ther, these experiments demonstrate that BMP-4 can act during gastrula tion both to promote ventral mesoderm differentiation and to attenuate dorsalizing signals derived from the organizer.