Abnormal lens morphogenesis and ectopic lens formation in the absence of β‐catenin function

Abstract

beta-Catenin plays a key role in cadherin-mediated cell adhesion as well as in canonical Wnt signaling. To study the role of beta-catenin during eye development, we used conditional Cre/loxP system in mouse to inactivate beta-catenin in developing lens and retina. Inactivation of beta-catenin does not suppress lens fate, but instead results in abnormal morphogenesis of the lens. Using BAT-gal reporter mice, we show that beta-catenin-mediated Wnt signaling is notably absent from lens and neuroretina throughout eye development. The observed defect is therefore likely due to the cytoskeletal role of beta-catenin, and is accompanied by impaired epithelial cell adhesion. In contrast, inactivation of beta-catenin in the nasal ectoderm, an area with active Wnt signaling, results in formation of crystallin-positive ectopic lentoid bodies. These data suggest that, outside of the normal lens, beta-catenin functions as a coactivator of canonical Wnt signaling to suppress lens fate.

The lens: a classical model of embryonic induction providing new insights into cell determination in early development

“…Conditional deletion of b-catenin, using the Lens-Cre construct, results in breaks in the continuous curve of the epithelium. These breaks corresponds to disruption of cytoskeletal and/or junctional complexes, detected by F-actin and ZO1 labelling, respectively [63,64]. These results indicate that Wnt independent b-catenin activity is required, not for lens fate decision or initial lens placodal invagination, but for further lens morphogenesis.…”

“…Although no activation of the canonical Wnt pathway has been detected in the developing lens [63,64], b-catenin is expressed in the lens placode at E9.5 [64], suggesting that Wnt independent b-catenin activity plays a role in lens formation. b-catenin is known to affect cell adhesion and morphogenesis, and is a central component of the cadherin-catenin adhesion complex, which anchors the adhesion complex to the actin cytoskeleton.…”

“…In LacZ reporter mouse lines, which express LacZ in response to activation of the canonical Wnt pathway [61,62] there is no indication of X-gal staining, i.e. Wnt activity, in the lens region at E8.5-E15.5 [63,64]. Consistently, even in the presence of Wnt inhibitors prospective lens cells in chick explants still upregulate the lens markers L-Maf and d-crystallin (Sjö dal and Gunhaga 2006, unpublished data).…”

Eye-specific expression of an ancestral jellyfish PaxB gene interferes with Pax6 function despite its conserved Pax6/Pax2 characteristics

“…To construct the PaxB transgene utilized here, three copies of mouse Pax6 lens-specific element (also known as ectoderm enhacer EE) (Williams et al, 1998) were cloned upstream of the Pax6 P0 minimal promoter as described for LR-Cre mice (Kreslova et al, 2007). We used this LR (lens, retina)-module to drive the expression of PaxB and Cre cDNAs connected via an internal ribosomal entry site (IRES) (Fig.…”

“…Paired-less Pax6 is likely involved in the cell fate Structure of Pax6, Pax2 and PaxB proteins; PaxB has a Pax2-like paired domain (red rectangle), a conserved octapeptide motif that is also present in Pax2 (yellow circle), and a Pax6-like homeodomain (blue rectangle) (A). Schematic diagram of the PaxB transgene Three copies of the lens-specific ectoderm enhancer (EE) derived from the Pax6 gene were cloned upstream of the Pax6 P0 minimal promoter (LR-module; Kreslova et al, 2007) to drive the expression of PaxB and Cre cDNAs connected via internal ribosomal entry site (IRES) (B). The onset of PaxB expression analyzed by whole mount RNA in situ hybridization at E9.5 (C,C',C'') and E10.5 (D,D',D'') embryos.…”