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A S. Menko, Michelle Leonard, Liping Zhang, Ni Zhai; Distinct Roles for N-cadherin-linked c-Src and Fyn Kinases in Regulating Lens Cell Differentiation and Morphogenesis. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5886.
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© ARVO (1962-2015); The Authors (2016-present)
In this study we dissect the functions of the individual Src family kinases (SFKs) c-Src and Fyn in epithelial cell differentiation and morphogenesis through studies with a classical developmental model, the embryonic chick lens.
Differentiation-state specific association of c-Src and Fyn with N-cadherin junctions and activation of N-cadherin-linked SFKs in the embryonic lens was determined by co-immunoprecipitation analysis. The role of Src kinases in both lens cadherin junction maturation and lens morphogenesis was determined by blocking SFK activity with the specific inhibitor PP1 and by knocking down c-Src or Fyn with an siRNA approach in lens cultures.
Our findings revealed that among the SFKs expressed by the lens only c-Src and Fyn were linked to N-cadherin junctions and that their association with N-cadherin was differentiation-state-specific. The SFK c-Src was most highly associated with N-cadherin in undifferentiated lens epithelial cells, while Fyn was most highly linked to N-cadherin in lens fiber cells undergoing morphogenesis in the cortical fiber zone. It was also specifically in undifferentiated lens epithelial cells and in cortical fiber cells that there was a high level of SFK activity associated with N-cadherin junctions. We discovered that inhibiting Src kinase activity in lens epithelial cells was permissive for their differentiation initiation, but that longer-term exposure of these cells to the SFK inhibitor prevented lens cells from completing their differentiation program by blocking their morphogenesis. These dichotomous roles of SFK signaling in lens differentiation and development were found to reflect distinct functions of the SFKs c-Src and Fyn. Knockdown of c-Src promoted the maturation of N-cadherin junctions, an event we have shown previously is required for lens epithelial cell compaction and the early stages of lens epithelial cell differentiation. In contrast, siRNA knockdown of Fyn blocked lens differentiation-specific gene expression and lens morphogenesis.
The Src kinases c-Src and Fyn have important roles in regulating lens cell differentiation and morphogenesis through their action at N-cadherin junctions.
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