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P. Westenskow, A. Mathiesen, M. Cordenonsi, S. Piccolo, F. Beermann, S. Fuhrmann; The Wnt/ß-Catenin Pathway Is Required for Retinal Pigmented Epithelium Development. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2914.
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© ARVO (1962-2015); The Authors (2016-present)
Wnts are secreted glycoproteins that signal through distinct pathways. The Wnt/ß-catenin signaling pathway regulates tissue patterning, cell fate specification, and proliferation during embryonic development. When Wnts bind the Frizzled receptors, ß-catenin accumulates in the cytoplasm and translocates to the nucleus where it associates with TCF/LEF family members to activate transcription of Wnt target genes. In the neural crest, TCF/LEF activates the pigment-specific transcription factor Mitf to promote pigment cell differentiation. We have previously reported that the pathway is transiently active in the developing retinal pigmented epithelium (RPE) based on data collected from mice harboring a ß-catenin inducible transgene. In the current study, our goal is to determine more precisely the role of Wnt/ß-catenin signaling during RPE development in mouse.
We are using a floxed ß-catenin construct and two RPE-specific Cre drivers (Tyrp1 and Dct) to conditionally inactivate the Wnt/ß-catenin pathway in the mouse optic cup. Mutant eyes are analyzed at embryonic and postnatal stages using histological and immunohistological techniques.
Very obvious defects in pigmentation and differentiation are apparent in the mutant eyes; for example, expression of the key transcription factors Mitf and Otx2 is downregulated in the affected RPE. We are currently analyzing expression of other eye-specific genes to further confirm these results. Since ß-catenin is also involved in cell adhesion, we are carefully analyzing whether cell adhesion defects contribute to the overall phenotype.
Our data strongly suggests that the Wnt/ß-catenin signaling pathway is required for RPE development in mouse. Our results will provide new insights into the mechanisms underlying RPE development in the mammalian eye.
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