Abstract
Wnt signaling orchestrates multiple aspects of central nervous system development, including cell proliferation and cell fate choices. In this study, we used gene transfer to activate or inhibit canonical Wnt signaling in vivo in the developing eye. We found that the expression of Wnt2b or constitutively active (CA) beta-catenin inhibited retinal progenitor gene (RPG) expression and the differentiation of retinal neurons. In addition, Wnt signal activation in the central retina was sufficient to induce the expression of markers of the ciliary body and iris, two tissues derived from the peripheral optic cup (OC). The expression of a dominant-negative (DN) allele of Lef1, or of a Lef1-engrailed fusion protein, led to the inhibition of expression of peripheral genes and iris hypoplasia, suggesting that canonical Wnt signaling is required for peripheral eye development. We propose that canonical Wnt signaling in the developing optic vesicle (OV) and OC plays a crucial role in determining the identity of the ciliary body and iris. Because wingless (wg) plays a similar role in the induction of peripheral eye tissues of Drosophila, these findings indicate a possible conservation of the process that patterns the photoreceptive and support structures of the eye.
Highlights
Organ formation requires the establishment of pattern in relatively broad domains, leading to specific fate choices by individual cells, along with coordinated proliferation
Wnt signal activation reduces retinal cell proliferation in explants and in vivo Clonal analysis of retinal reaggregation cultures treated with Wnt2bconditioned medium showed that Wnt2b can stimulate the proliferation of E5 RPCs in vitro (Kubo et al, 2003)
Wnt signal mediates peripheral eye development observation that Wnt2b inhibits the expression of Notch and proneural genes in the retina led to the proposal that Wnt2b keeps RPCs undifferentiated in the peripheral optic cup (OC) (Kubo et al, 2005)
Summary
Organ formation requires the establishment of pattern in relatively broad domains, leading to specific fate choices by individual cells, along with coordinated proliferation. The eye field comprises groups of cells biased to develop into various eye structures. It is specified in the anterior neural plate, and evaginates to form the OV, which in turn invaginates to form the OC. A third region, the peripheral rim of the OC, forms two of the peripheral support tissues, the ciliary body and the iris (Beebe, 1986). These tissues are composed of a non-pigmented inner layer, which is continuous with the NR, and a pigmented outer layer, which is continuous with the RPE.
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