Co-operative roles for E-cadherin and N-cadherin during lens vesicle separation and lens epithelial cell survival

Abstract

The classical cadherins are known to have both adhesive and signaling functions. It has also been proposed that localized regulation of cadherin activity may be important in cell assortment during development. In the context of eye development, it has been suggested that cadherins are important for separation of the invaginated lens vesicle from the surface ectoderm. To test this hypothesis, we conditionally deleted N-cadherin or E-cadherin from the presumptive lens ectoderm of the mouse. Conditional deletion of either cadherin alone did not produce a lens vesicle separation defect. However, these conditional mutants did exhibit common structural deficits, including microphthalmia, severe iris hyperplasia, persistent vacuolization within the fibre cell region, and eventual lens epithelial cell deterioration. To assess the co-operative roles of E-cadherin and N-cadherin within the developing lens, double conditional knockout embryos were generated. These mice displayed distinct defects in lens vesicle separation and persistent expression of another classical cadherin, P-cadherin, within the cells of the persistent lens stalk. Double mutant lenses also exhibited severe defects in lens epithelial cell adhesion and survival. Finally, the severity of the lens phenotype was shown to be sensitive to the number of wild-type E- and N-cadherin alleles. These data suggest that the co-operative expression of both E- and N-cadherin during lens development is essential for normal cell sorting and subsequent lens vesicle separation.

Stage-dependent modes of Pax6-Sox2 epistasis regulate lens development and eye morphogenesis

“…7R,S) was retained. Furthermore, in AP2α-cre; Ncad Fl/Fl embryos, as expected (Pontoriero et al, 2009), we observed a failure of the lens vesicle to separate from the surface ectoderm and a persistence of P-cadherin expression ( Fig. 7O,P).…”

“…Sox1 is first expressed later during invagination of the lens placode, and also during lens morphogenesis in lens fiber cells (Kamachi et al, 1998). Sox2 has been implicated in lens development through its regulation of the δ1-crystallin gene in the chick (Kamachi et al, 2001) and, more recently, of N-cadherin (Matsumata et al, 2005), an adhesion molecule known to be required for normal lens morphogenesis and the differentiation of lens fiber cells (Pontoriero et al, 2009). It has also been proposed that the Sox2 gene is regulated by the Sox2 protein product in combination with Pax6 through the N-3 enhancer that is active in the presumptive lens (Inoue et al, 2007).…”

Deletion of Autophagy-related 5 (Atg5) and Pik3c3 Genes in the Lens Causes Cataract Independent of Programmed Organelle Degradation

“…The abnormal development of the entire eyeball, including the retina and iris in Pik3c3 flox/flox ;MLR10-Cre mice, may be a secondary result of impaired lens development, as similar phenotypes were reported in other mouse models with lens-specific deletion of fibroblast growth factor receptor (33), PKC (34), ␤1-integrin (35), ␤-catenin (36), and N/E-cadherin (55). Alternatively, it may be due to an off-target effect of MLR10-Cre expression in non-lens tissues in the eye.…”

Pitx3 directly regulates Foxe3 during early lens development

“…These cells do not elongate and differentiate into primary lens fibers as seen in the wild-type lenses. E-cadherin is an epithelial marker , Pontoriero et al, 2009, Zeisberg and Neilson, 2009 whose expression is suppressed in the differentiating epithelial cells in wild-type lenses. Such persistent ectopic expression of E-cadherin and AP-2a has also been observed in Prox1 knockout mice (Wigle et al, 1999).…”