Fibroblast growth factor receptor signaling is essential for lens fiber cell differentiation.
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 alpha-, beta- and gamma-crystallins. Therefore, while signaling by FGF receptors is essential for lens fiber differentiation, different FGF receptors function redundantly.
Zhao
Haotian
H
Graduate Program in Molecular, Cellular and Developmental Biology, College of Biological Sciences, The Ohio State University, Columbus, OH 43210, USA.
Yang
Tianyu
T
Madakashira
Bhavani P
BP
Thiels
Cornelius A
CA
Bechtle
Chad A
CA
Garcia
Claudia M
CM
Zhang
Huiming
H
Yu
Kai
K
Ornitz
David M
DM
Beebe
David C
DC
Robinson
Michael L
ML
D000818:Animals; D002454:Cell Differentiation; D049108:Cell Enlargement; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000378:metabolism; D005124:Eye Abnormalities / Q000196:embryology; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018390:Gene Targeting; D018398:Homeodomain Proteins / Q000378:metabolism; D007908:Lens, Crystalline / Q000166:cytology / Q000196:embryology*; D051379:Mice; D009154:Mutation; D051257:Proto-Oncogene Proteins c-maf / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
C493961:Cdkn1b protein, mouse; C493965:Cdkn1c protein, mouse; D050761:Cyclin-Dependent Kinase Inhibitor p57; D018398:Homeodomain Proteins; C495608:Maf protein, mouse; D051257:Proto-Oncogene Proteins c-maf; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; D050760:Cyclin-Dependent Kinase Inhibitor p27; D005346:Fibroblast Growth Factors; C496349:Fgfr1 protein, mouse; C496354:Fgfr2 protein, mouse; C496366:Fgfr3 protein, mouse; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3