Xenopus frizzled 7 can act in canonical and non-canonical Wnt signaling pathways: implications on early patterning and morphogenesis

Abstract

Here we report the cloning of a Xenopus frizzled transmembrane receptor, Xfz7, and describe its expression pattern during early embryogenesis. Xfz7 mRNA is provided maternally and zygotic transcription peaks in gastrula stages. At that time, transcripts are preferentially localized to the marginal zone and become restricted to distinct regions of the tadpoles in tailbud stages. Overexpression of Xfz7 in embryos perturbs the morphogenesis of trunk and tail, blocks convergence-extension movements in animal caps induced with activin and dorsal lip explants and decreases cadherin-mediated cell adhesion. Xfz7 can interact specifically with Xwnt-8b and signal in the canonical, dorsalizing Wnt pathway. Overexpression of Xfz7 does not trigger the Wnt-1-type pathway but acts in a non-canonical Wnt or morphogenetic-effector pathway involving the activation of protein kinase C (PKC). Xfz7 seems to be involved in different aspects of Wnt signaling during the course of embryogenesis.

Essential role of non-canonical Wnt signalling in neural crest migration

“…Inhibition of canonical Wnt signalling by a dominant-negative form of Tcf3 does not inhibit neural crest migration (F. Romero and R.M., unpublished). There is convincing experimental evidence that shows that canonical Wnt signalling is involved in neural crest induction and cell differentiation (Dorsky et al, 1998;Garcia-Castro et al, 2002;LaBonne and Bronner-Fraser, 1998;Lee et al, 2004 (CarreiraBarbosa et al, 2003;Djiane et al, 2000;Kuhl et al, 2000;Medina et al, 2000;Sumanas and Ekker, 2001;Wang and Malbon, 2004;Winklbauer et al, 2001). We have shown that Fz7 is expressed in the premigratory neural crest just before migration, as well as in the migrating neural crest.…”

“…Although no specific Wnt11 receptor has been identified, there is some evidence that suggests that PCP Wnt signalling involves Fz7 (Carreira-Barbosa et al, 2003;Djiane et al, 2000;Medina et al, 2000;Sumanas and Ekker, 2001;Winklbauer et al, 2001). We examined the distribution of the Fz7 receptor in neural crest cells.…”

“…For injections and lineage tracing, mRNA was resuspended in DEPC-water, and co-injected into two-or eight-cell-stage embryos with fluorescein dextran or rhodamine dextran (FDX, RDX; Molecular Probes) using 8-12 nl needles as described by Aybar et al (Aybar et al, 2003). The constructs used were Slug (Mayor et al, 1995); Wnt11 (Ku and Melton, 1993); Fz7 (Medina et al, 2000); dd1 and dd2 (Sokol, 1996); and Dsh-∆N, Dsh-DEP+ and dnWnt11 .…”

JNK and ROKα function in the noncanonical Wnt/RhoA signaling pathway to regulate Xenopus convergent extension movements

“…The specific domains of Dsh, PDZ, and DEP, are required for the Wnt/ PCP pathway in CE movements during vertebrate gastrulation (Djiane et al, 2000;Heisenberg et al, 2000;Medina et al, 2000;Tada and Smith, 2000;Wallingford et al, 2000). The DEP domain deletion mutant of Dsh (Dsh-⌬DEP) has DN effects on JNK activation (Boutros et al, 1998;Li et al, 1999;Moriguchi et al, 1999) and regulation of CE movements in the Wnt/PCP pathway Wallingford et al, 2000).…”

“…For example, Wnt-11 regulates CE movements by means of Frizzled (Fz) and Dishevelled (Dsh; Heisenberg et al, 2000;Tada and Smith, 2000), which resembles PCP signaling pathway in flies. Furthermore, the specific domains of Dsh (Wharton, 2003) required for PCP signaling in CE movements during vertebrate gastrulation (Djiane et al, 2000;Heisenberg et al, 2000;Medina et al, 2000;Tada and Smith, 2000;Wallingford et al, 2000) are identical to those required in Drosophila (Axelrod et al, 1998;Boutros et al, 1998;Boutros and Mlodzik, 1999). In addition, CE movements in both Xenopus and zebrafish are controlled by the core PCP genes, including RhoA/Rac1 (Habas et al, 2001(Habas et al, , 2003Tahinci and Symes, 2003), JNK (Yamanaka et al, 2002), Rho-associated kinase-2 (ROK2, Marlow et al, 2002), Strabismus (Stbm, Darken et al, 2002;Goto and Keller, 2002;Jessen et al, 2002;Park and Moon, 2002), and Prickle (Takeuchi et al, 2003;Veeman et al, 2003a).…”