The homeobox gene Six3 is a potential regulator of anterior segment formation in the chick eye

Yi Wen Hsieh, Xiang Mei Zhang, Eddie Lin, Guillermo Oliver, Xian Jie Yang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)265-280
Number of pages16
JournalDevelopmental Biology
Volume248
Issue number2
DOIs
StatePublished - 2002

Funding

We thank Drs. Randy L. Johnson, Cliff Tabin, and Peter Gruss for providing cDNAs, and Francesca Pignoni and Larry Zipursky for communicating unpublished data and for discussion. We also thank Kristin Schmidt for her excellent technical support. This work was supported in part by grants from the Research to Prevent Blindness Foundation, the March of Dimes Birth Defect Foundation, the Karl Kirchgessner Foundation, and the NIH (EY12270) (to X.-J.Y.), and by grants from NIH (EY12162 and GM58462) and the American Lebanese Syrian Associated Charities (ALSAC) (to G.O.).

Keywords

  • Anterior segment
  • Chick
  • Development
  • Eye
  • Mesenchyme
  • Misexpression
  • Six3

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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