Defective FGF signaling causes coloboma formation and disrupts retinal neurogenesis  

作　　者：Shuyi Chen Hua Li Karin Gaudenz Ariel Paulson Fengli Guo Rhonda Trimble Allison Peak Christopher Seidel Chuxia Deng Yasuhide Furuta Ting Xie 

机构地区：[1]Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA [2]Department of Anatomy and Cell Biology, University of Kansas School of Medicine, 3901 Rainbow Blvd, Kansas City, KS 66160, USA [3]Genetics of Development and Disease Branch, NIDDK, NIH, 10/9/N105, Bethesda, MD 20892, US [4]Department of Biochemistry and Molecular Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA

出　　处：《Cell Research》2013年第2期254-273,共20页细胞研究（英文版）

摘　　要：The optic fissure （OF） is a transient opening on the ventral side of the developing vertebrate eye that closes before nearly all retinal progenitor cell differentiation has occurred. Failure to close the OF results in coloboma, a congenital disease that is a major cause of childhood blindness. Although human genetic studies and animal models have linked a number of genes to coloboma, the cellular and molecular mechanisms driving the closure of the OF are still largely unclear. In this study, we used Cre-LoxP-mediated conditional removal of fibroblast growth factor （FGF） receptors, Fgfrl and Fgfr2, from the developing optic cup （OC） to show that FGF signaling regulates the closing of the OF. Our molecular, cellular and transcriptome analyses of Fgfrl and Fgfr2 double conditional knockout OCs suggest that FGF signaling controls the OF closure through modulation of retinal progenitor cell proliferation, fate specification and morphological changes. Furthermore, Fgfrl and Fgfr2 double conditional mutant retinal progenitor cells fail to initiate retinal ganglion cell （RGC） genesis. Taken together, our mouse genetic studies reveal that FGF signaling is es-sential for OF morphogenesis and RGC development.The optic fissure （OF） is a transient opening on the ventral side of the developing vertebrate eye that closes before nearly all retinal progenitor cell differentiation has occurred. Failure to close the OF results in coloboma, a congenital disease that is a major cause of childhood blindness. Although human genetic studies and animal models have linked a number of genes to coloboma, the cellular and molecular mechanisms driving the closure of the OF are still largely unclear. In this study, we used Cre-LoxP-mediated conditional removal of fibroblast growth factor （FGF） receptors, Fgfrl and Fgfr2, from the developing optic cup （OC） to show that FGF signaling regulates the closing of the OF. Our molecular, cellular and transcriptome analyses of Fgfrl and Fgfr2 double conditional knockout OCs suggest that FGF signaling controls the OF closure through modulation of retinal progenitor cell proliferation, fate specification and morphological changes. Furthermore, Fgfrl and Fgfr2 double conditional mutant retinal progenitor cells fail to initiate retinal ganglion cell （RGC） genesis. Taken together, our mouse genetic studies reveal that FGF signaling is es-sential for OF morphogenesis and RGC development.

关 键 词：optic fissure COLOBOMA FGF signaling retinal ganglion cells 

分 类 号：Q516[生物学—生物化学] TP311.56[自动化与计算机技术—计算机软件与理论]