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Dev Biol October 1, 2006; 298 (1): 71-86.

Neural induction in Xenopus requires inhibition of Wnt-beta-catenin signaling.

Heeg-Truesdell E , LaBonne C .

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.

PubMed ID: 16879817
Article link: Dev Biol
Grant support: [+]
Genes referenced: acta4 actc1 actl6a ascl2 dll1 egr2 en2 foxg1 gal.2 hes5.2 hesx1 lef1 msx1 muc2 muc2l myc neurog1 nog nrp1 otx2 pax6 six1 snai2 sox2 sox3 sox9 tcf3 tcf7l1 tubb2b zic1
Morpholinos: ctnnb1 MO1

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