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Z. Cai, G. Feng, X. Zhang; Shp2 Mediated FGF-Ras Signaling Is Required for Optic Vesicle Patterning But Not Retinal Differentiation Wave. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4812.
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From Drosophila to mammals, the retina develops in a conserved wave-like pattern emanating from optic stalk to peripheral region. While Drosophila retinal differentiation is regulated by Hedgehog and Receptor Tyrosine Kinase (RTK) signaling in a sequential-induction fashion, whether such mechanism applies to vertebrate retinal development remains controversial. Previous studies have also implicated Fibroblast Growth Factor (FGF) signaling in specifying retina versus retinal pigmented epithelium (RPE) fate during early eye development, but the molecular mechanism of such profound effect of FGF signaling is still lacking. Shp2 protein tyrosine phosphatase is a critical mediator of many RTK pathways, including FGF signaling. We would therefore like to determine the mechanism of FGF signaling in retinal development by studying the genetic ablation of Shp2.
Mouse genetic models were generated to determine the temporal and spatial requirement of Shp2 in retinal development and the genetic interaction between Shp2 with downstream Ras signaling.
By conditional inactivating Shp2, we showed the Shp2 is required for FGF induced MAPK signaling during retinal development. However, contrary to the view that FGF signaling controls the wave-like neurogenesis pattern in retina, we demonstrated that the Shp2 mutant clones in retina did not prevent the initiation or propagation of retinal differentiation wave. Instead, through a series of Shp2 ablation mutants, we established that Shp2 dependent FGF signaling was specifically required for the patterning of optic vesicle into retinal pigmented epithelial and neural retina, but not the subsequent retinal differentiation. Finally, we showed that gain-of-function of mutation in Ras can rescue the retinal defects in the Shp2 mutants.
FGF/Shp2/Ras signaling is specifically required for the early patterning of optic vesicle, but not the retinal differentiation wave.
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