Defective FGF signaling causes coloboma formation and disrupts retinal neurogenesis
| Autor: | Fengli Guo, Hua Li, Ting Xie, Allison Peak, Ariel Paulson, Karin Gaudenz, Shuyi Chen, Christopher Seidel, Rhonda Trimble, Chu-Xia Deng, Yasuhide Furuta |
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| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Retinal Ganglion Cells
medicine.medical_specialty Cellular differentiation Neurogenesis Biology Fibroblast growth factor Retina chemistry.chemical_compound Mice Internal medicine Conditional gene knockout medicine Animals Receptor Fibroblast Growth Factor Type 1 Receptor Fibroblast Growth Factor Type 2 Molecular Biology Mice Knockout Coloboma Gene Expression Profiling Stem Cells Retinal Cell Biology medicine.disease Cell biology Fibroblast Growth Factors Endocrinology medicine.anatomical_structure chemistry Retinal ganglion cell Original Article sense organs Signal Transduction |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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