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Fibroblast growth factor receptor signaling is essential for lens fiber cell differentiation |
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| Authors: | Zhao Haotian Yang Tianyu Madakashira Bhavani P Thiels Cornelius A Bechtle Chad A Garcia Claudia M Zhang Huiming Yu Kai Ornitz David M Beebe David C Robinson Michael L |
| Institution: | a Graduate Program in Molecular, Cellular and Developmental Biology, College of Biological Sciences, The Ohio State University, Columbus, OH 43210, USA b Department of Pathology, College of Medicine, The Ohio State University, Columbus, OH 43210, USA c Department of Pediatrics, College of Medicine, The Ohio State University, Columbus, OH 43210, USA d Department of Ophthalmology and Visual Sciences, Washington University Medical School, St. Louis, MO 63110, USA e Department of Molecular Biology and Pharmacology, Washington University Medical School, St. Louis, MO 63110, USA f Division of Human and Molecular Genetics, Columbus Children's Research Institute, 700 Children's Dr. Columbus, OH 43205, USA g Department of Zoology, Miami University, Oxford, OH 45056, USA |
| Abstract: | The vertebrate lens provides an excellent model to study the mechanisms that regulate terminal differentiation. Although fibroblast growth factors (FGFs) are thought to be important for lens cell differentiation, it is unclear which FGF receptors mediate these processes during different stages of lens development. Deletion of three FGF receptors (Fgfr1-3) early in lens development demonstrated that expression of only a single allele of Fgfr2 or Fgfr3 was sufficient for grossly normal lens development, while mice possessing only a single Fgfr1 allele developed cataracts and microphthalmia. Profound defects were observed in lenses lacking all three Fgfrs. These included lack of fiber cell elongation, abnormal proliferation in prospective lens fiber cells, reduced expression of the cell cycle inhibitors p27kip1 and p57kip2, increased apoptosis and aberrant or reduced expression of Prox1, Pax6, c-Maf, E-cadherin and α-, β- and γ-crystallins. Therefore, while signaling by FGF receptors is essential for lens fiber differentiation, different FGF receptors function redundantly. |
| Keywords: | Apoptosis Cell cycle FGF receptor Lens development Lens fiber differentiation Redundancy Conditional knockout |
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