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.

Independent degeneration of photoreceptors and retinal pigment epithelium in conditional knockout mouse models of choroideremia

“…Six3 is a homeobox transcription factor that is expressed in the neuroretina during eye development (30,31). Consistent with this, we did not observe depigmentation of the RPE nor abnormal cells next to the RPE in Figure 2).…”

Effects of High Salt-Exposure on the Development of Retina and Lens in 5.5-Day Chick Embryo

“…Loss of Pax6 function leads to an eyeless phenotype in mice [33,34]. When periocular mesenchyme cells, originating from the neural crest and expressing Pax-6, are experimentally reduced, this leads to anterior eye defects in the chick eye morphogenesis [20]. We could show that retinal Pax6 expression was impaired in high salt-treated chick embryos.…”

“…HNK-1 is mainly expressed in migratory neural crest cells which contribute to the head mesenchyme [18,19]. The complex role of Pax6 in eye development is also conserved in the chick embryo [20]. …”

Anterior segment development relevant to glaucoma

“…Many of the same genes and interactions are conserved between flies and vertebrates (Oliver et al, 1995, Pignoni et al, 1997, Xu et al, 1997, Heanue et al, 1999, Kozmik et al, 1999, Xu et al, 1999a, Xu et al, 1999b, Heanue et al, 2002, Hsieh et al, 2002. Therefore, mammalian orthologues of the fly genes are good candidates to participate in anterior segment development and may contribute to ASD and glaucoma.…”