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Dev Biol 2015 Nov 01;4071:131-44. doi: 10.1016/j.ydbio.2015.08.001.
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G protein-coupled receptors Flop1 and Flop2 inhibit Wnt/β-catenin signaling and are essential for head formation in Xenopus.

Miyagi A , Negishi T , Yamamoto TS , Ueno N .

Patterning of the vertebrate anterior-posterior axis is regulated by the coordinated action of growth factors whose effects can be further modulated by upstream and downstream mediators and the cross-talk of different intracellular pathways. In particular, the inhibition of the Wnt/β-catenin signaling pathway by various factors is critically required for anterior specification. Here, we report that Flop1 and Flop2 (Flop1/2), G protein-coupled receptors related to Gpr4, contribute to the regulation of head formation by inhibiting Wnt/β-catenin signaling in Xenopus embryos. Using whole-mount in situ hybridization, we showed that flop1 and flop2 mRNAs were expressed in the neural ectoderm during early gastrulation. Both the overexpression and knockdown of Flop1/2 resulted in altered embryonic head phenotypes, while the overexpression of either Flop1/2 or the small GTPase RhoA in the absence of bone morphogenetic protein (BMP) signaling resulted in ectopic head induction. Examination of the Flops' function in Xenopus embryo animal cap cells showed that they inhibited Wnt/β-catenin signaling by promoting β-catenin degradation through both RhoA-dependent and -independent pathways in a cell-autonomous manner. These results suggest that Flop1 and Flop2 are essential regulators of Xenopus head formation that act as novel inhibitory components of the Wnt/β-catenin signaling pathway.

PubMed ID: 26244992
Article link: Dev Biol

Species referenced: Xenopus laevis
Genes referenced: bcr cer1 chrd ctnnb1 cyp26a1 dvl2 en2 foxg1 gpr4 gpr4l gpr4l.2 has1 nppa otx2 pnp psmd6 rho rhoa shh snai2 tbl1x wnt8a
Antibodies: Cdh3 Ab1
Morpholinos: flop2 MO1 mgc69520 MO2

Phenotypes: Xla Wt + XB5959819 [provisional] (fig.3.b) [+]

Article Images: [+] show captions