Purchase this article with an account.
Revathi Balasubramanian, Chenqi Tao, Karina Polanco, Xin Zhang; Identifying the role of Sox2 in mediating FGF-WNT signaling interaction in the developing ciliary margin.. Invest. Ophthalmol. Vis. Sci. 2019;60(9):6026.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The developing peripheral neural retina also called the ciliary margin differentiates into the ciliary body and the iris. Aberrations in development of the ciliary margin causes pathologies such as aniridia and congenital glaucoma. The development of the ciliary margin is not completely understood.
In our study, we use conditional loss-of-function and gain-of-function mouse models of FGF and WNT signaling to dissect their roles in the developing ciliary margin. We also use genetic approaches to identify the mechanism of interaction between FGF and WNT signaling pathways.
We find that loss of FGF signaling in the peripheral retina causes ectopic expansion of the distal ciliary margin in the developing optic cup. Loss of FGF signaling in the developing peripheral retina leads to aniridia in the adult. We identified Fgf9 and Fgf3 as important ligands in facilitating FGF signaling via the MAPK-ERK pathway in the peripheral retina. Meanwhile, loss of WNT signaling in the peripheral retina causes a loss of distal ciliary margin domain. Conditional expression of both FGF and WNT results in the trans-differentiation of the retinal pigment epithelium into a ciliary margin like structure. Loss of FGF signaling in the peripheral retina results in the loss of Sox2 expression placing Sox2 downstream of FGF signaling. Additionally, over-expression of Sox2 on an FGF deficient background inhibits WNT pathway genes.
FGF and WNT signaling interaction at the peripheral retina is crucial for the development of the ciliary margin. We also find that Sox2 acting downstream of FGF signaling, limits WNT signaling in the peripheral retina, providing insights into the FGF-WNT signaling interaction at the ciliary margin.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
This PDF is available to Subscribers Only