Abstract
Purpose: :
To study the role of the high–mobility–group transcription factor Sox11 during development of the anterior eye segment.
Methods: :
The ocular phenotype of mutant, Sox11–deficient Sox–/– mice was investigated from embryonic day (E) 9.5 until birth. Activity of the Sox11 promoter during eye development of Sox–/– and Sox+/– mice was assessed by staining for beta–galactosidase, and the expression of Pax6 by immunohistochemistry. BrdU–labeling was used to study cell proliferation. The expression of BMP7 and TGF–beta2 in Sox–/– mice, and of Sox11 in Pax6–/– mice was investigated by Northern blotting and real time RT–PCR. In vitro transfection experiments were used to study the influence of Pax6 on Sox11 expression.
Results: :
During anterior eye development, the Sox11 promoter is active in cells of the optic vesicle, the surface ectoderm and the ocular mesenchyme. Sox11–deficient mice show a complex defect in anterior eye development including delay of lens formation, Peters’ anomaly and anterior coloboma. Defects in lens formation are associated with reduced mitotic activity in surface ectoderm and lens vesicle. No changes in the expression of Pax6 are observed in Sox–/– mice, while the expression of Sox11 is reduced in Pax6–/– mice. In vitro transfection experiments show an increase in Sox11 expression when higher doses of Pax6 are present. In Sox–/– mice, the expression of BMP7, but not that of TGF–beta2, is markedly reduced during anterior eye development.
Conclusions: :
Sox11 is required during separation of the lens vesicle from the surface ectoderm and the closure of the anterior hyaloid fissure. The expression of Sox11 is under control of Pax6. Changes in BMP7–signalling are involved in the effects of Sox11 on anterior eye development.
Keywords: development • transcription factors • transgenics/knock-outs