title: Anterior segment dysgenesis in the eyes of mice deficient for the high-mobility-group transcription factor Sox11.
abstract: We describe that Sox11, a member of the group C of the Sox transcription factor family, is critically required during the morphogenetic processes of early eye development, and that lack of Sox11 results in ocular anterior segment dysgenesis (ASD). Sox11-deficient mice show a persistent lens stalk, a delay in lens formation, and the phenotypes of Peters' anomaly and microphthalmia at birth. In addition, the optic fissure does not close in the anterior halves of the eyes resulting in anterior coloboma. The delay in lens formation is associated with a reduced mitotic activity in the lens placode during its invagination into the optic cup. No changes in Pax6 expression are observed in the developing eyes of Sox11-/- mice, whereas the expression of Sox11 is reduced in optic cup, optic vesicle and lens placode of Pax6+/- embryos and in the optic vesicle of Pax6-/- mice. Transfection experiments show an increase in Sox11 expression when higher doses of Pax6 are present. Considerably smaller amounts of BMP7 are expressed in lens and optic cup of Sox11-/- mice as compared to their wild-type littermates. We conclude that Sox11 is required during separation of the lens vesicle from the surface ectoderm and the closure of the anterior optic fissure. The expression of Sox11 in early eye development is under control of Pax6, and changes in BMP7-signalling appear to be involved in the effects of Sox11 on anterior eye development. Our findings suggest that SOX11 might similarly be involved in the pathogenesis of ASD in human patients.
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg, Regensburg, Germany.
authors.forename: Antje
authors.initials: A
authors.lastname: Wurm
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sock
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fuchshofer
authors.forename: Michael
authors.initials: M
authors.lastname: Wegner
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
mesh_terms: D000818:Animals; D000869:Anterior Eye Segment / Q000002:abnormalities* / Q000473:pathology; D015153:Blotting, Western / Q000379:methods; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D003103:Coloboma / Q000235:genetics / Q000473:pathology; D005136:Eye Proteins / Q000502:physiology; D047109:Fetal Development; D006609:High Mobility Group Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D018398:Homeodomain Proteins / Q000502:physiology; D007908:Lens, Crystalline / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008850:Microphthalmos / Q000235:genetics / Q000473:pathology; D008938:Mitosis; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000502:physiology; D055751:SOXC Transcription Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D005136:Eye Proteins; D006609:High Mobility Group Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; C000605732:Pax6 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D055751:SOXC Transcription Factors; C490793:Sox11 protein, mouse; D016212:Transforming Growth Factor beta