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Rethinking Wnt antagonists?

Wnt family members, such as Wingless, regulate cell fate and cell behaviour by binding to G-protein-coupled Frizzled (Fz) receptors, activating a canonical signalling pathway that stabilizes the transcription factor b-catenin and non-canonical mechanisms such as the planar cell polarity pathway. Secreted Fz-related proteins (SFRPs) antagonize Wnt signalling and are thought to function as competitive inhibitors that prevent Wnt molecules from interacting with Fz receptors. Work by Paola Bovolenta and co-workers, however, indicates that their mode of action might actually be more complex (see p. 2471). Using in vitro and in vivo approaches, they demonstrate that, during chick retinal development, SFRP1 promotes retinal ganglion and cone photoreceptor cell generation while inhibiting generation of amacrine cells. Interestingly, SFRP1 appears to promote retinal cell differentiation without affecting b-catenin-dependent transcription; in fact, the authors find that canonical Wnt signalling does not seem to operate in these cells under normal conditions. They implicate inhibition of glycogen synthase kinase 3b (usually a consequence of Wnt action rather than Wnt antagonism) in the SFRP1 effect. The authors therefore suggest that Wnt-independent mechanisms of SRFP1 action exist, perhaps involving direct binding of SFRP1 to Fz receptors.

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Related articles in JCS:

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

Pilar Esteve, Françoise Trousse, Josana Rodríguez, and Paola Bovolenta
JCS 2003 116: 2471-2481. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?