Interaction of Wnt and caudal-related genes in zebrafish posterior body formation

Abstract

Although Wnt signaling plays an important role in body patterning during early vertebrate embryogenesis, the mechanisms by which Wnts control the individual processes of body patterning are largely unknown. In zebrafish, wnt3a and wnt8 are expressed in overlapping domains in the blastoderm margin and later in the tailbud. The combined inhibition of Wnt3a and Wnt8 by antisense morpholino oligonucleotides led to anteriorization of the neuroectoderm, expansion of the dorsal organizer, and loss of the posterior body structure-a more severe phenotype than with inhibition of each Wnt alone-indicating a redundant role for Wnt3a and Wnt8. The ventrally expressed homeobox genes vox, vent, and ved mediated Wnt3a/Wnt8 signaling to restrict the organizer domain. Of posterior body-formation genes, expression of the caudal-related cdx1a and cdx4/kugelig, but not bmps or cyclops, was strongly reduced in the wnt3a/wnt8 morphant embryos. Like the wnt3a/wnt8 morphant embryos, cdx1a/cdx4 morphant embryos displayed complete loss of the tail structure, suggesting that Cdx1a and Cdx4 mediate Wnt-dependent posterior body formation. We also found that cdx1a and cdx4 expression is dependent on Fgf signaling. hoxa9a and hoxb7a expression was down-regulated in the wnt3a/wnt8 and cdx1a/cdx4 morphant embryos, and in embryos with defects in Fgf signaling. Fgf signaling was required for Cdx-mediated hoxa9a expression. Both the wnt3a/wnt8 and cdx1a/cdx4 morphant embryos failed to promote somitogenesis during mid-segmentation. These data indicate that the cdx genes mediate Wnt signaling and play essential roles in the morphogenesis of the posterior body in zebrafish.

Wnt Signaling in Vertebrate Axis Specification

“…Further supporting this hypothesis, TCF-dependent reporter activity and the nuclear localization of endogenous b-catenin are elevated in the anterior-toposterior gradient (Kiecker and Niehrs 2001;Dorsky et al 2002). The critical role of Wnt signaling in anteroposterior axis specification has been corroborated by depletion experiments for pathway components Erter et al 2001;Lekven et al 2001;Shimizu et al 2005;Bellipanni et al 2006;Hikasa et al 2010) and the analysis of the corresponding zebrafish mutations. Headless (hdl) was identified as a point mutation in a tcf3 gene homolog, which represses Wnt target genes in zebrafish embryos (Kim et al 2000).…”

A direct role for Wnt8 in ventrolateral mesoderm patterning

“…Other studies have suggested that Wnt signaling prevents posterior mesoderm progenitor differentiation, thereby maintaining a posterior mesoderm progenitor pool (Shimizu et al, 2005;Thorpe et al, 2005;Martin and Kimelman, 2008;Row and Kimelman, 2009). This suggests an additional role for wnt8 wherein BMPs are necessary for the maintenance of the tailbud, but the release of progenitors into presomitic mesoderm is a Wntregulated process.…”

“…The mesodermal phenotype of wnt8 mutants could be explained by two alternative hypotheses: on the one hand, mesoderm dorsalization may result in specification of fewer ventrolateral/posterior mesoderm progenitors, thereby restricting the progenitor pool that contributes to ventral and posterior fates. On the other hand, Wnt signaling may have a role in promoting the maintenance or expansion of posterior mesoderm progenitors, for example through cdx or no tail/brachyury gene regulation (Shimizu et al, 2005;Thorpe et al, 2005;Martin and Kimelman, 2008).…”

Wnt signaling through T-cell factor phosphorylation

“…The Cdx (caudal) and the Meis group genes, like Vent genes, are regulated by Wnt signaling during anteroposterior patterning [129][130][131] and contain multiple TCF-binding sites in their DNA regulatory elements [132][133][134]. Like Vent genes, these genes are also controlled by TCF3-mediated repression [79].…”