Double assurance in the induction of axial development by egg dorsal determinants in Xenopus embryos

We recently reported that microinjection of Xenopus nodal- related (xnr) mRNAs into beta- catenin- depleted Xenopus embryos rescued a complete dorsal axis. Xnrs mediate the signal of the Nieuwkoop center that induces the Spemann-Mangold organizer in the overlying mesoderm, a process inhibited by the Nodal antagonist Cerberus-short (CerS). However, beta- catenin also induces a second signaling center in the dorsal prospective ectoderm, designated the Blastula Chordin and Noggin Expression (BCNE) center, in which the homeobox gene siamois (sia) plays a major role. In this study, we asked whether the Xnrs and Sia depend on each other or function on parallel pathways. Expression of both genes induced beta- catenin- depleted embryos to form complete axes with heads and eyes via the activation of similar sets of downstream organizer- specific genes. Xnrs did not activate siamois, and, conversely, Sia did not activate xnrs, although both were induced by beta- catenin stabilization. Depletion with morpholinos revealed a robust role for the downstream target Chordin. Remarkably, Chordin depletion prevented all ectopic effects resulting from microinjection of the mRNA encoding the maternal cytoplasmic determinant Huluwa, including the radial expansion of brain tissue and the ectopic expression of the ventral gene sizzled. The main conclusion was that the BCNE and Nieuwkoop centers provide a double assurance mechanism for axial formation by independently activating similar downstream transcriptional target gene repertoires. We suggest that Siamois likely evolved from an ancestral Mix- type homeodomain protein called Sebox as a Xenopus- specific adaptation for the rapid differentiation of the anterior neural plate in the ectoderm.