Purchase this article with an account.
R. De Iongh, H. Brown, J.W. McAvoy; Expression of Focal Adhesion Kinase (FAK) in the Murine Lens . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4492.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose: Focal adhesion kinase (FAK) has been implicated in many biological activities including cell proliferation, migration, differentiation and apoptosis. In this study we investigated the expression of FAK during normal lens development and in two mouse models of abnormal lens development, which are characterised by abnormal cell proliferation, migration, differentiation and apoptosis.Methods: Embryonic and postnatal ocular tissues were obtained from wild-type (FVB/N) and transgenic mice that expressed ectopically either a truncated type II TGFß receptor (ove591) or constitutively-active TGFß1 (ove853), under the control of the αA-crystallin promoter. FAK expression was investigated by in-situ hybridisation (ISH), immuno-histochemistry (IHC) and by Western blot (WB). As FAK can be expressed as alternatively spliced forms, ISH was carried out using two probes coding for 5' and 3' regions of the cDNA. Similarly, IHC and WB were carried out using both N-terminal and C-terminal antibodies. Results: By ISH both riboprobes showed FAK was expressed weakly in the epithelium and strongly in the transitional zone from E11.5 to P3. By P21, expression of FAK mRNA had decreased in the epithelium but was still strongly expressed at the equator and in the transitional zone. Western blots of neonatal lens (P0-P4) extracts showed FAK was expressed predominantly as a 125kD species. IHC (at age P1-P21), using both N-terminal and C-terminal antibodies showed that FAK protein was most strongly localised in the transitional zone and in outer cortical fibres. Little or no FAK immunoreactivity was detected in the epithelium. Reactivity for FAK was detected in TGFß-induced cataractous epithelial plaques of ove853 mice. Some abnormal localisations of FAK were also detected in the deep cortical fibres of ove591 mice, adjacent to degenerate nuclear fibres. Conclusions: FAK is expressed predominantly at the equator and in the transitional zone during normal lens development, suggesting a role in cell movement and differentiation. FAK expression in TGFß-induced epithelial plaques suggests it may play a role in this epithelial-mesenchymal transition. Additionally, its expression in fibres undergoing apoptosis due to inhibition of TGFß signalling suggests it may play a role during the phase of terminal fibre differentiation that is regulated by TGFß.
This PDF is available to Subscribers Only