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First published online 30 April 2003
doi: 10.1242/jcs.00452

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SFRP1 modulates retina cell differentiation through a ß-catenin-independent mechanism

Departamento de Neurobiología del Desarrollo, Instituto Cajal, CSIC, Dr Arce 37, Madrid 28002, Spain

^* Author for correspondence (e-mail: bovolenta{at}cajal.csic.es)

Accepted 7 March 2003

Secreted frizzled related proteins (SFRPs) are soluble molecules capable of binding WNTS and preventing the activation of their canonical signalling cascade. Here we show that Sfrp1 contributes to chick retina differentiation with a mechanism that does not involve modifications in the transcriptional activity of ß-catenin. Thus, addition of SFRP1 to dissociated retinal cultures or retroviral mediated overexpression of the molecule consistently promoted retinal ganglion and cone photoreceptor cell generation, while decreasing the number of amacrine cells. Measure of the activity of the ß-catenin-responsive Tcf-binding site coupled to a luciferase reporter in transiently transfected retinal cells showed that Sfrp1 was unable to modify the basal ß-catenin transcriptional activity of the retina cells. Interestingly, a dominant-negative form of GSK3ß gave similar results to those of Sfrp1, and a phosphorylation-dependent inhibition of GSK3ß activity followed SFRP1 treatment of retina cells. Furthermore, retroviral mediated expression of a dominant-negative form of GSK3ß induced a retina phenotype similar to that observed after Sfrp1 overexpression, suggesting a possible involvement of this kinase in SFRP1 function.

Key words: Chick, Eye development, Retina ganglion cells, Wnt signalling, GSK3ß

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