title: Defective FGF signaling causes coloboma formation and disrupts retinal neurogenesis.
abstract: 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, Fgfr1 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 Fgfr1 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, Fgfr1 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 essential for OF morphogenesis and RGC development.
authors.affiliation: Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA. sch@stowers.org
authors.forename: Shuyi
authors.initials: S
authors.lastname: Chen
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Karin
authors.initials: K
authors.lastname: Gaudenz
authors.forename: Ariel
authors.initials: A
authors.lastname: Paulson
authors.forename: Fengli
authors.initials: F
authors.lastname: Guo
authors.forename: Rhonda
authors.initials: R
authors.lastname: Trimble
authors.forename: Allison
authors.initials: A
authors.lastname: Peak
authors.forename: Christopher
authors.initials: C
authors.lastname: Seidel
authors.forename: Chuxia
authors.initials: C
authors.lastname: Deng
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Furuta
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
mesh_terms: D000818:Animals; D003103:Coloboma / Q000378:metabolism* / Q000473:pathology; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D020869:Gene Expression Profiling; D051379:Mice; D018345:Mice, Knockout; D055495:Neurogenesis; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D005346:Fibroblast Growth Factors; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2