Journal of Cell Science 116, e1203 (2003)
Copyright © 2003 The Company of Biologists Limited
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.
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]
