ABSTRACT

The Xenopus laevis gastrula is the organism of choice to discover the molecular mechanisms of dorsal-ventral (D-V) tissue differentiation. Making use of the rich heritage of experimental embryology bequeathed by the Spemann-Mangold 1924 dorsal organizer transplantation experiment, a morphogenetic gradient generated by a biochemical pathway of extracellular molecules was identified. This chapter discusses how saturating molecular screens isolated novel molecules from the Spemann organizer that are secreted BMP antagonists, such as Noggin, Follistatin, and Chordin. The head-inducer Cerberus is a Nodal inhibitor (and in addition inhibits Wnt and BMP). A large number of Wnt antagonists are also secreted by the dorsal organizer, such as Dickkopf, Frzb-1, Crescent, Angptl-4, Pkdcc, and Bighead. For every action on the dorsal side, there is a reaction on the ventral side that ensures a self-organizing system. In the ventral center BMP4/7 signaling is highest (while it is lowest at the opposite dorsal side), activating a synexpression group of BMP target genes that include Xvent1/2, BAMBI, Xolloid-related, Sizzled, Twisted gastrulation, and Crossveinless-2. Cell lineage studies show that, remarkably, Xenopus embryos bisected at blastula self-organize the missing half by relocalization of the dorsal and ventral centers, followed by histotypic induction through the action of the Spemann organizer.