Deficient FGF signaling causes optic nerve dysgenesis and ocular coloboma

• DOI: 10.1242/dev.089987
• Publication Date: 2013-05-30T01:44:23Z
• Authors: Zhigang Cai; Chenqi Tao; Hongge Li; Raj Ladher; Noriko Gotoh; Gen-Sheng Feng; Fen Wang; Xin Zhang
• Keywords: Coloboma; Optic vesicle; Optic cup (embryology); Dysgenesis

FGF signaling plays a pivotal role in eye development. Previous studies using vitro chick models and systemic zebrafish mutants have suggested that is required for the patterning specification of optic vesicle, but due to lack genetic models, its mammalian retinal development remains elusive. In this study, we show specific deletion Fgfr1 Fgfr2 vesicle disrupts ERK signaling, which results disc nerve dysgenesis and, ultimately, ocular coloboma. Defective does not abrogate Shh or BMP nor it affect axial vesicle. Instead, regulates Mitf Pax2 coordinating closure fissure specification, necessary outgrowth nerve. Genetic evidence further supports formation an Frs2α-Shp2 complex recruitment receptors are crucial downstream process, whereas constitutively active Ras can rescue coloboma mutants. Our thus reveal previously unappreciated FGF-Frs2α-Shp2-Ras-ERK axis preventing These findings suggest components pathway may be novel targets diagnosis therapeutic interventions congenital anomalies.