Defective FGF signaling causes coloboma formation and disrupts retinal neurogenesis View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-02

AUTHORS

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

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. More... »

PAGES

254

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cr.2012.150

DOI

http://dx.doi.org/10.1038/cr.2012.150

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1012862639

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23147794


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