Transcription factor GATA-3 is essential for lens development.
During vertebrate lens development, the anterior, ectoderm-derived lens vesicle cells differentiate into a monolayer of epithelial cells that retain proliferative potential. Subsequently, they exit the cell cycle and give rise to posterior lens fiber cells that form the lens body. In the present study, we demonstrate that the transcription factor GATA-3 is expressed in the posterior lens fiber cells during embryogenesis, and that GATA-3 deficiency impairs lens development. Interestingly, expression of E-cadherin, a premature lens vesicle marker, is abnormally prolonged in the posterior region of Gata3 homozygous mutant lenses. Furthermore, expression of gamma-crystallin, a differentiation marker for fiber cells, is reduced. This suppressed differentiation is accompanied by an abnormal cellular proliferation, as well as with diminished levels of the cell-cycle inhibitors Cdkn1b/p27 and Cdkn1c/p57 and increased Ccnd2/cyclin D2 abundance. Thus, these observations suggest that GATA-3 is essential for lens cells differentiation and proper cell cycle control.
Maeda
Atsuko
A
Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan.
Moriguchi
Takashi
T
Hamada
Michito
M
Kusakabe
Manabu
M
Fujioka
Yuki
Y
Nakano
Takako
T
Yoh
Keigyou
K
Lim
Kim-Chew
KC
Engel
James Douglas
JD
Takahashi
Satoru
S
D000818:Animals; D017209:Apoptosis; D015820:Cadherins / Q000235:genetics / Q000502:physiology; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D056742:Cyclin D2; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000502:physiology; D016213:Cyclins / Q000235:genetics / Q000502:physiology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020287:In Situ Nick-End Labeling; D007908:Lens, Crystalline / Q000166:cytology / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038222:gamma-Crystallins / Q000235:genetics / Q000502:physiology
D015820:Cadherins; C486196:Ccnd2 protein, mouse; C493961:Cdkn1b protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D038222:gamma-Crystallins; D050760:Cyclin-Dependent Kinase Inhibitor p27