Neural induction in Xenopus requires inhibition of Wnt-β-catenin signaling

Abstract

Canonical Wnt signals have been implicated in multiple events during early embryogenesis, including primary axis formation, neural crest induction, and A-P patterning of the neural plate. The mechanisms by which Wnt signals can direct distinct fates in cell types that are closely linked both temporally and spatially remains poorly understood. However, recent work has suggested that the downstream transcriptional mediators of this pathway, Lef/Tcf family DNA binding proteins, may confer distinct outcomes on these signals in some cellular contexts. In this study, we first examined whether inhibitory mutants of XTcf3 and XLef1 might block distinct Wnt-dependent signaling events during the diversification of cell fates in the early embryonic ectoderm. We found that a Wnt-unresponsive mutant of XTcf3 potently blocks neural crest formation, whereas an analogous mutant of XLef1 does not, and that the difference in activity mapped to the C-terminus of the proteins. Significantly, the inhibitory XTcf3 mutant also blocked expression of markers of anterior-most cell types, including cement gland and sensory placodes, indicating that Wnt signals are required for rostral as well as caudal ectodermal fates. Unexpectedly, we also found that blocking canonical Wnt signals in the ectoderm, using the inhibitory XTcf3 mutant or by other means, dramatically expanded the size of the neural plate, as evidenced by the increased expression of early pan-neural markers such as Sox3 and Nrp1. Conversely, we find that upregulation of canonical Wnt signals interferes with the induction of the neural plate, and this activity can be separated experimentally from Wnt-mediated neural crest induction. Together these findings provide important and novel insights into the role of canonical Wnt signals during the patterning of vertebrate ectoderm and indicate that Wnt inhibition plays a central role in the process of neural induction.

BMP inhibition initiates neural induction via FGF signaling and Zic genes

“…First, Smad5-sbn induces neural tissue in the absence of dorsal mesoderm markers, making indirect neural induction in our paradigm highly unlikely. Second, the lack of repression of chordin and goosecoid expression by Smad5-sbn indicates that it does not inhibit Wnt and Nodal signaling, which are known to regulate these genes and limit neural specification (11,19,20). Therefore, in absence of current contradictory evidence, we suggest that Smad5-sbn acts as a specific and powerful BMP inhibitor.…”

Mechanisms driving neural crest induction and migration in the zebrafish andXenopus laevis

“…That said, inhibition of canonical Wnt signaling appears to be required for neural induction. 120 In the embryo, both the requirement for Wnt signaling (for neural crest induction) and its inhibition (in neuroectoderm) are likely to be influenced by the presence of the B1-type Sox proteins, Sox2 and Sox3 (Fig. 5).…”

Maintaining embryonic stem cell pluripotency with Wnt signaling

“…In support of Wnt signaling having a role in maintaining the pluripotency of mouse ES cells, the genetic ablation of both Gsk3a and Gsk3b or the pharmacological inhibition of GSK3 in these cells promotes their self-renewal and blocks neural differentiation (Aubert et al, 2002;Doble et al, 2007;Haegele et al, 2003;Sato et al, 2004;Ying et al, 2008). Consistent with this notion, experiments in Xenopus and mouse embryos have revealed that Wnt signaling prevents neural development (Haegele et al, 2003;Heeg-Truesdell and LaBonne, 2006;Itoh and Sokol, 1999;Yoshikawa et al, 1997).…”