Functions of the FGF signaling pathway during the optic fissure closure

Dissertation (Ph.D.)--University of Kansas, Anatomy & Cell Biology, 2007.The mammalian eye represents an excellent model system to study tissue morphogenesis and cell fate determination in the nervous system. During mammalian eye development, the optic fissure (OF), a transient opening on the ventral side of the optic cup, provides an entry site for the mesenchymal cells to migrate into the eye to form hyaloid vessels for blood supply in the developing eye. The OF is then closed but leaves a permanent opening in the posterior, which is known as the optic disc, following the migration of the mesenchymal cells. The failure in the OF closure causes the formation of coloboma, which affects 2.6 babies per 10,000 births. However, the molecular and cellular mechanisms that control the OF closure are still obscure. In my dissertation study, I have carefully documented, for the first time, the process of the OF closure. Then, I have used the conditional knockout of Fgfr1 and 2 specifically from the developing eye to demonstrate that FGF signaling is required for controlling the OF closure. The eyes which are absent of functions of Fgfr1 and 2 develop coloboma. Furthermore, I have shown that FGF signaling regulates the proliferation, cell fate switches and morphological changes of OF progenitor cells. Finally, FGF signaling is also required for the formation of the optic disc and the maintenance of the optic stalk. Therefore, the knowledge gained from this study has provided novel insight into the cellular and molecular mechanisms underlying the OF closure and possibly coloboma formation in humans