Fibroblast growth factor receptor signaling is essential for lens fiber cell differentiation

• Published in: Developmental biology 2008-06, Vol.318 (2), p.276-288
• Main 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.
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Cell cycle; Cell Differentiation; Cell Enlargement; Conditional knockout; Cyclin-Dependent Kinase Inhibitor p27 - metabolism; Cyclin-Dependent Kinase Inhibitor p57 - metabolism; Eye Abnormalities - embryology; FGF receptor; Fibroblast Growth Factors - metabolism; Gene Targeting; Homeodomain Proteins - metabolism; Lens development; Lens fiber differentiation; Lens, Crystalline - cytology; Lens, Crystalline - embryology; Mice; Mutation; Proto-Oncogene Proteins c-maf - metabolism; Receptor, Fibroblast Growth Factor, Type 1 - genetics; Receptor, Fibroblast Growth Factor, Type 1 - metabolism; Receptor, Fibroblast Growth Factor, Type 2 - genetics; Receptor, Fibroblast Growth Factor, Type 2 - metabolism; Receptor, Fibroblast Growth Factor, Type 3 - genetics; Receptor, Fibroblast Growth Factor, Type 3 - metabolism; Redundancy; Signal Transduction; Tumor Suppressor Proteins - metabolism
• ISSN: 0012-1606; 1095-564X
• DOI: 10.1016/j.ydbio.2008.03.028

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 p27 kip1 and p57 kip2, 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.