A role for Wnt/beta-catenin signaling in lens epithelial differentiation.
The differentiation of epithelial cells and fiber cells from the anterior and posterior compartments of the lens vesicle, respectively, give the mammalian lens its distinctive polarity. While much progress has been made in understanding the molecular basis of fiber differentiation, little is known about factors that govern the differentiation of the epithelium. Members of the Wnt growth factor family appear to be key regulators of epithelial differentiation in various organ systems. Wnts are ligands for Frizzled receptors and can activate several signaling pathways, of which the best understood is the Wnt/beta-catenin pathway. The presence of LDL-related protein coreceptors (LRPs) 5 or 6 has been shown to be a requirement for Wnt signaling through the beta-catenin pathway. To access the role of this signaling pathway in the lens, we analyzed mice with a null mutation of lrp6. These mice had small eyes and aberrant lenses, characterized by an incompletely formed anterior epithelium resulting in extrusion of the lens fibers into the overlying corneal stroma. We also showed that multiple Wnts, including 5a, 5b, 7a, 7b, 8a, 8b, and Frizzled receptors 1, 2, 3, 4, and 6, were detected in the lens. Expression of these molecules was generally present throughout the lens epithelium and extended into the transitional zone, where early fiber elongation occurs. In addition to both LRP5 and LRP6, we also showed the expression of other molecules involved in Wnt signaling and its regulation, including Dishevelleds, Dickkopfs, and secreted Frizzled-related proteins. Taken together, these results indicate a role for Wnt signaling in regulating the differentiation and behavior of lens cells.
Stump
Richard J W
RJ
Save Sight Institute, The University of Sydney, Sydney Hospital & Eye Hospital, GPO Box 4337, NSW 2006, Australia.
Ang
Sharyn
S
Chen
Yongjuan
Y
von Bahr
Tatiana
T
Lovicu
Frank J
FJ
Pinson
Kathleen
K
de Iongh
Robbert U
RU
Yamaguchi
Terry P
TP
Sassoon
David A
DA
McAvoy
John W
JW
D000818:Animals; D002454:Cell Differentiation; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004847:Epithelial Cells / Q000166:cytology; D051157:Frizzled Receptors; D026502:LDL-Receptor Related Proteins; D007908:Lens, Crystalline / Q000166:cytology*; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D051379:Mice; D011506:Proteins / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011973:Receptors, LDL / Q000502:physiology; D015534:Trans-Activators / Q000502:physiology*; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C495267:CTNNB1 protein, mouse; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D051157:Frizzled Receptors; D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555483:Lrp5 protein, mouse; C555484:Lrp5 protein, rat; C555476:Lrp6 protein, mouse; C555477:Lrp6 protein, rat; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011973:Receptors, LDL; D015534:Trans-Activators; D051153:Wnt Proteins; C490603:Wnt8b protein, mouse; D029961:Zebrafish Proteins; D051176:beta Catenin