title: The homeobox gene Six3 is a potential regulator of anterior segment formation in the chick eye.
abstract: The anterior segment of the vertebrate eye consists of highly organized and specialized ocular tissues critical for normal vision. The periocular mesenchyme, originating from the neural crest, contributes extensively to the anterior segment. During chick eye morphogenesis, the homeobox gene Six3 is expressed in a subset of periocular mesenchymal cells and in differentiating anterior segment tissues. Retrovirus-mediated misexpression of Six3 causes eye anterior segment malformation, including corneal protrusion and opacification, ciliary body and iris hypoplasia, and trabecular meshwork dysgenesis. Histological and molecular marker analyses demonstrate that Six3 misexpression disrupts the integrity of the corneal endothelium and the expression of extracellular matrix components critical for corneal transparency. Six3 misexpression also leads to a reduction of the periocular mesenchymal cell population expressing Lmx1b, Pitx2, and Pax6, transcription factors critical for eye anterior segment morphogenesis. Moreover, elevated levels of Six3 attenuate proliferation of periocular mesenchymal cells in vitro and differentiating anterior segment tissues in vivo. These results suggest that, in addition to its function in eye primordium determination, Six3 plays a role in regulating the development of the vertebrate eye anterior segment.
authors.affiliation: Department of Ophthalmology, Jules Stein Eye Institute, University of California-Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Hsieh
authors.forename: Xiang-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Eddie
authors.initials: E
authors.lastname: Lin
authors.forename: Guillermo
authors.initials: G
authors.lastname: Oliver
authors.forename: Xian-Jie
authors.initials: XJ
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation; D002455:Cell Division; D002642:Chick Embryo; D003315:Cornea / Q000166:cytology / Q000378:metabolism; D005123:Eye / Q000196:embryology* / Q000378:metabolism*; D005124:Eye Abnormalities / Q000235:genetics; D005136:Eye Proteins; D018507:Gene Expression Regulation, Developmental; D005901:Glaucoma; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D009024:Morphogenesis; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000097607:Homeobox Protein SIX3
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000097607:Homeobox Protein SIX3