Downstream of β-catenin: A positive feedback loop between Goosecoid and Nodals in Spemann’s organizer

We report on the role of the homeobox gene goosecoid ( gsc ) within an epistatic pathway that mediates body axis formation in Xenopus . Embryos depleted of β-catenin form exclusively ventral structures and lack all traces of axial structures. Microinjection of gsc mRNA rescues an entire body axis with head and trunk-tail. This remarkable activity is shared with the homeobox gene siamois ( sia ) and growth factors of the Nodal family. Using a Gsc antisense morpholino, we showed that dorsalization by Xenopus nodal-related 6 mRNA has a strong requirement for Gsc in β-catenin depleted embryos. These experiments uncovered a positive feedback loop between Gsc and Nodal that is required downstream of β-catenin for the maintenance of dorsal and anterior tissues during gastrulation in endomesoderm. The Gsc-Xnr feedback loop leads to the expression of Spemann organizer genes that antagonize signals from ventral tissues. Similarly, rescue of β-catenin depletion by murine β-catenin mRNA also has a requirement for Gsc. Although gsc is a gene conserved throughout the animal kingdom during evolution, its loss-of-function during mouse gastrulation has only very weak phenotypic effects; perhaps the redundancy described here in Xenopus might be part of the explanation. The functional pathway defined here is self-organizing and robust as required to form a perfect embryo time after time.