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Genes Dev 2008 Nov 01;2221:3050-63. doi: 10.1101/gad.1687308.
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Sfrp5 coordinates foregut specification and morphogenesis by antagonizing both canonical and noncanonical Wnt11 signaling.

Li Y , Rankin SA , Sinner D , Kenny AP , Krieg PA , Zorn AM .

Cell identity and tissue morphogenesis are tightly orchestrated during organogenesis, but the mechanisms regulating this are poorly understood. We show that interactions between Wnt11 and the secreted Wnt antagonist secreted frizzled-related protein 5 (Sfrp5) coordinate cell fate and morphogenesis during Xenopus foregut development. sfrp5 is expressed in the surface cells of the foregut epithelium, whereas wnt11 is expressed in the underlying deep endoderm. Depletion of Sfrp5 results in reduced foregut gene expression and hypoplastic liver and ventral pancreatic buds. In addition, the ventral foregut cells lose adhesion and fail to form a polarized epithelium. We show that the cell fate and epithelial defects are due to inappropriate Wnt/beta-catenin and Wnt/PCP signaling, respectively, both mediated by Wnt11. We provide evidence that Sfrp5 locally inhibits Wnt11 to maintain early foregut identity and to allow an epithelium to form over a mass of tissue undergoing Wnt-mediated cell movements. This novel mechanism coordinating canonical and noncanonical Wnt signaling may have broad implications for organogenesis and cancer.

PubMed ID: 18981481
PMC ID: PMC2577796
Article link: Genes Dev
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actb actl6a cdh3 ctnna1 ctnnb1 dkk1 dvl2 foxa2 frzb fubp1 fzd7 hhex hnf1b hnf4a itgb1 jun mapk8 myc nkx2-5 nr1h5 odc1 pdx1 prkci sfrp5 szl tbx2 tnni3 ventx2.2 wnt11 wnt11b wnt2b wnt4 wnt5a wnt5b wnt7b wnt8a
Antibodies: Cdh1 Ab1 Cdh3 Ab1 Ctnnb1 Ab2 Itgb1 Ab1
Morpholinos: sfrp5 MO1 sfrp5 MO2 sfrp5 MO5 wnt11b MO1

Phenotypes: Xla Wt + Mmu.lef1-Mmu.ctnnb1-GR + DEX (fig 6.d,e) [+]

Article Images: [+] show captions
References [+] :
Axelrod, Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways. 1998, Pubmed, Xenbase