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S. Chen, T. Johnson, R. McKay, C. Deng, Y. Furuta, N. Zhang, T. Xie; FGF Signaling Controls the Retinal Fissure Closure by Orchestrating Proliferation, Cell Fate Switches and Morphological Changes. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1319.
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Coloboma is a congenital disease, which is caused by the failure in closing the optic fissure (OF), a transient opening on the ventral side of the developing eye. Although mutations in several genes are known to cause coloboma, the cellular mechanisms underlying coloboma formation remain obscure. In this study, we use Fgfr conditional knockout mouse eyes as model to study the molecular and cellular mechanisms underlining the coloboma formation.
We used Cre-LoxP system to conditionally knockout Fgfr1 and Fgfr2 from developing mouse eye. E10.5 to E12 embryonic eyes are subjected to immunohistochemistry, in situ hybridization and microarray analysis to reveal the cellular and molecular mechanisms that lead to coloboma phenotype developed in Fgfr mutant eyes.
. Conditional knockout of Fgfr1 and Fgfr2 function specifically from the optic cup causes the formation of coloboma. We also have observed the retarded retinal cell proliferation, an error in cell fate switch of OF progenitor cells and failures in cell shape changes in Fgfr mutant eyes.
Our results indicate that retinal cell proliferation, cell fate switches and dynamic changes in cell shapes appear to drive the OF closure, and FGF signaling is involved in controlling the OF closing process by orchestrating these events. The celluar mechanisms contributing to coloboma formation revealed in mice will be useful for understanding how coloboma develops in humans
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