TY - JOUR
T1 - Fibroblast growth factor receptor signaling is essential for lens fiber cell differentiation
AU - Zhao, Haotian
AU - Yang, Tianyu
AU - Madakashira, Bhavani P.
AU - Thiels, Cornelius A.
AU - Bechtle, Chad A.
AU - Garcia, Claudia M.
AU - Zhang, Huiming
AU - Yu, Kai
AU - Ornitz, David M.
AU - Beebe, David C.
AU - Robinson, Michael L.
N1 - Funding Information:
The authors thank Ying Yang, Lindsay Wallace, Brad D. Wagner, J. Tommy Barrs, and Florinda Jaynes for technical assistance. We are grateful to Drs. Milan Jamrich, Paul Overbeek and J. Samuel Zigler for probes, plasmids and antibodies. We are indebted to Drs. Michael Weinstein and Chu-Xia Deng for Fgfr3-null mice and Drs. Janet Rossant and Juha Partanen for mice with conditional mutations in Fgfr1, Dr. David Cunningham for insightful discussions and suggestions, Michael Elnitsky and Timothy Muir for statistical consultation and Dr. Katia Del Rio-Tsonis for critical review of the manuscript. This work was supported by a grant from the National Eye Institute R01EY012995, a Miami University Undergraduate Research Award to Cornelius A. Thiels and by core facilities funded, in part, by The National Cancer Institute P30CA16058, Columbus Children's Research Institute and The Department of Zoology at Miami University.
PY - 2008/6/15
Y1 - 2008/6/15
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cell cycle
KW - Conditional knockout
KW - FGF receptor
KW - Lens development
KW - Lens fiber differentiation
KW - Redundancy
UR - http://www.scopus.com/inward/record.url?scp=44349136203&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2008.03.028
DO - 10.1016/j.ydbio.2008.03.028
M3 - Article
C2 - 18455718
AN - SCOPUS:44349136203
SN - 0012-1606
VL - 318
SP - 276
EP - 288
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -