SFRP1 modulates retina cell differentiation through a beta-catenin-independent mechanism.
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 beta-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 beta-catenin-responsive Tcf-binding site coupled to a luciferase reporter in transiently transfected retinal cells showed that Sfrp1 was unable to modify the basal beta-catenin transcriptional activity of the retina cells. Interestingly, a dominant-negative form of GSK3beta gave similar results to those of Sfrp1, and a phosphorylation-dependent inhibition of GSK3beta activity followed SFRP1 treatment of retina cells. Furthermore, retroviral mediated expression of a dominant-negative form of GSK3beta induced a retina phenotype similar to that observed after Sfrp1 overexpression, suggesting a possible involvement of this kinase in SFRP1 function.
Departamento de Neurobiología del Desarrollo, Instituto Cajal, CSIC, Dr Arce 37, Madrid 28002, Spain.
Pilar
P
Esteve
Françoise
F
Trousse
Josana
J
Rodríguez
Paola
P
Bovolenta
D025042:Amacrine Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D002478:Cells, Cultured; D002642:Chick Embryo; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D000099274:Frizzled-Related Proteins
D003598:Cytoskeletal Proteins; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D006023:Glycoproteins; D047908:Intracellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D000099274:Frizzled-Related Proteins