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Revathi Balasubramanian, Chenqi Tao, Karina Polanco, Xin Zhang; FGF and WNT Signaling Pathways Synergize During Ciliary Margin Development. Invest. Ophthalmol. Vis. Sci. 2018;59(9):322.
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The mammalian ciliary margin is a part of the developing peripheral neural retina that differentiates into the ciliary body and the iris. Congenital forms of aniridia and glaucoma exhibit pathologies in the iris and ciliary body respectively. The development of the ciliary margin and hence that of the ciliary body and the iris are poorly understood.
We use in vivo conditional knock-out and gain-of-function mouse models of FGF and WNT signaling to dissect the individual and combined contributions of both FGF and WNT signaling to the developing ciliary margin.
We find that loss of FGF signaling in the peripheral retina causes ectopic expansion of the ciliary margin in the developing optic cup which translates to aniridia at later stages. We also find that loss of WNT signaling in the peripheral retina causes loss of ciliary margin domain in a manner complementary to that of FGF signaling and translates to ciliary body hypoplasia at later stages. Meanwhile, loss of both FGF and WNT signaling together at the peripheral retina phenocopies the loss of WNT signaling indicating that FGF acts upstream over WNT signaling to inhibit WNT signaling in the peripheral retina. Using gain-of-function mouse models, we show that regulated levels of both FGF and WNT signaling are needed for the development of the ciliary margin.
We show that WNT and FGF signaling gradients synergize at the peripheral retina leading to the specification of the ciliary margin. Our results also show that FGF and WNT signaling levels need to be regulated to allow for the acquisition of ciliary margin cell fate over a neural retinal or retinal pigment epithelial fate, during development. This work helps us understand the interaction between FGF and WNT signaling moieties in the development of iris and ciliary body.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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