Wnt ligands from the embryonic surface ectoderm regulate ‘bimetallic strip’ optic cup morphogenesis in mouse

April C. Carpenter, April N. Smith, Heidi Wagner, Yamit Cohen-Taya, Sujata Rao, Valerie Wallace, Ruth Ashery-Padan, Richard A. Lang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


TheWnt/β-catenin response pathway is central tomany developmental processes. Here, we assessed the role of Wnt signaling in early eye development using the mouse as a model system. We showed that the surface ectoderm region that includes the lens placode expressed 12 out of 19 possible Wnt ligands. When these activities were suppressed by conditional deletion of wntless (Le-cre; Wlsfl/fl) there were dramatic consequences that included a saucer-shaped optic cup, ventral coloboma, and a deficiency of periocular mesenchyme. This phenotype shared features with that produced when the Wnt/β-catenin pathway co-receptor Lrp6 is mutated or when retinoic acid (RA) signaling in the eye is compromised. Consistent with this, microarray and cell fate marker analysis identified a series of expression changes in genes known to be regulated byRAor by theWnt/β-catenin pathway. Using pathway reporters, we showed that Wnt ligands from the surface ectoderm directly or indirectly elicit a Wnt/β-catenin response in retinal pigment epithelium(RPE) progenitors near the optic cup rim. In Le-cre; Wlsfl/fl mice, the numbers ofRPEcells are reduced and this can explain, using the principle of the bimetallic strip, the curvature of the optic cup. These data thus establish a novel hypothesis to explain how differential cell numbers in a bilayered epithelium can lead to shape change.

Original languageEnglish
Pages (from-to)972-982
Number of pages11
JournalDevelopment (Cambridge)
Issue number5
StatePublished - 2015


FundersFunder number
National Institutes of Health
National Eye InstituteR01EY016241
National Institute of Arthritis and Musculoskeletal and Skin DiseasesP30AR047363


    • Morphogenesis
    • Optic cup
    • Wnt ligands


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