Volume 23, No 2, Feb 2013
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 23 Issue 2, February 2013: 254-273
ORIGINAL ARTICLES
Defective FGF signaling causes coloboma formation and disrupts retinal neurogenesis
Shuyi Chen1,2, Hua Li1, Karin Gaudenz1, Ariel Paulson1, Fengli Guo1, Rhonda Trimble1, Allison Peak1, Christopher Seidel1, Chuxia Deng3, Yasuhide Furuta4 and Ting Xie1,2
1Stowers Institute for Medical Research, 1000 East 50th Street, Kansas City, MO 64110, USA
2Department of Anatomy and Cell Biology, University of Kansas School of Medicine, 3901 Rainbow Blvd, Kansas City, KS 66160, USA
3Genetics of Development and Disease Branch, NIDDK, NIH, 10/9/N105, Bethesda, MD 20892, USA
4Department of Biochemistry and Molecular Biology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA
Correspondence: Shuyi Chen, Ting Xie(sch@stowers.org; tgx@stowers.org)
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.
Cell Research (2013) 23:254–273; doi:10.1038/cr.2012.150; published online 13 November 2012
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