Mapping Canonical Wnt Signaling in the Developing and Adult Retina

Liu, Hong; Thurig, Sherry; Mohamed, Othman A.; Dufort, Daniel; Wallace, Valerie A.

doi:10.1167/iovs.06-0403

Cited by 97 publications

(121 citation statements)

References 86 publications

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“…3a). In contrast to corneal studies, the role of WNT signaling in the posterior pole has been examined in various parts of the tissue, such as the neural retina, retinal vasculature and retinal pigment epithelium [24][25][26][27][28] . To evaluate the expression pattern of WNT7B in the posterior pole of eyes, we examined the localization of WNT7B in the mouse eye.…”

Section: Resultsmentioning

confidence: 99%

Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia

et al. 2015

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Myopia can cause severe visual impairment. Here, we report a two-stage genome-wide association study for three myopia-related traits in 9,804 Japanese individuals, which was extended with trans-ethnic replication in 2,674 Chinese and 2,690 Caucasian individuals. We identify WNT7B as a novel susceptibility gene for axial length (rs10453441, P meta ¼ 3.9 Â 10 À 13 ) and corneal curvature (P meta ¼ 2.9 Â 10 À 40 ) and confirm the previously reported association between GJD2 and myopia. WNT7B significantly associates with extreme myopia in a case-control study with 1,478 Asian patients and 4,689 controls (odds ratio (OR) meta ¼ 1.13, P meta ¼ 0.011). We also find in a mouse model of myopia downregulation of WNT7B expression in the cornea and upregulation in the retina, suggesting its possible role in the development of myopia.

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Section: Resultsmentioning

confidence: 99%

Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia

et al. 2015

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“…There is substantial evidence that the Wnt signaling pathway controls the development of peripheral eye structures in several animal models (8,12,(18)(19)(20). TSK is expressed in the peripheral region of the developing chick eye at E6 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…5 R-U). Normal development of peripheral eye structures is also regulated by Wnt signaling (10)(11)(12)31), with Wnt2b and Fzd4 acting as the primary Wnt ligand and receptor in this context. In situ hybridization analysis of the expression pattern of Wnt2b and Fzd4 at E15.5 eye showed increased and expanded expression of both these genes in the peripheral eye of TSK −/− mice compared with WT mice (Fig.…”

Section: Wnt-3amentioning

confidence: 99%

Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b for binding to transmembrane protein Frizzled4

Ohta

Ito

Kuriyama

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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The Wnt signaling pathway is essential for the development of diverse tissues during embryogenesis. Signal transduction is activated by the binding of Wnt proteins to the type I receptor lowdensity lipoprotein receptor-related protein 5/6 and the seven-pass transmembrane protein Frizzled (Fzd), which contains a Wntbinding site in the form of a cysteine-rich domain. Known extracellular antagonists of the Wnt signaling pathway can be subdivided into two broad classes depending on whether they bind primarily to Wnt or to low-density lipoprotein receptor-related protein 5/6. We show that the secreted protein Tsukushi (TSK) functions as a Wnt signaling inhibitor by binding directly to the cysteine-rich domain of Fzd4 with an affinity of 2.3 × 10 −10 M and competing with Wnt2b. In the developing chick eye, TSK is expressed in the ciliary/iris epithelium, whereas Wnt2b is expressed in the adjacent anterior rim of the optic vesicle, where it controls the differentiation of peripheral eye structures, such as the ciliary body and iris. TSK overexpression effectively antagonizes Wnt2b signaling in chicken embryonic retinal cells both in vivo and in vitro and represses Wnt-dependent specification of peripheral eye fates. Conversely, targeted inactivation of the TSK gene in mice causes expansion of the ciliary body and upregulation of Wnt2b and Fzd4 expression in the developing peripheral eye. Thus, we uncover a crucial role for TSK as a Wnt signaling inhibitor that regulates peripheral eye formation. eye development | signaling modulator | small leucine-rich proteoglycan

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“…Furthermore, tissues surrounding the CE express sFRP1 and sFRP2, which antagonize Wnt signaling by sequestering Wnt ligands [32,33]. Consequently, we examined the Wnt signaling pathway as an additional inhibition of adult RSC proliferation.…”

Section: Sfrp2 Modulates Rsc Proliferationmentioning

confidence: 99%

Bone morphogenetic proteins and secreted frizzled related protein 2 maintain the quiescence of adult mammalian retinal stem cells

et al. 2013

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Rare retinal stem cells (RSCs) within the ciliary epithelium at the retinal margin of the adult mouse and human eyes can divide in vitro in the absence of growth factors to generate clonal, self-renewing spheres which can generate all the retinal cell types. Since no regenerative properties are seen in situ in the adult mammalian eye, we sought to determine the factors that are involved in the repression of endogenous RSCs. We discovered that factors secreted by the adult lens and cornea block the proliferation of adult RSCs in vitro. Bone morphogenetic protein (BMP)2, BMP4, and secreted frizzled related protein 2 were identified as principal effectors of the anti-proliferative effects on RSCs. As a similar induced quiescence was observed in vitro on both mouse and human RSCs, targeting these molecules in vivo may reactivate RSCs directly in situ in the eyes of the blind.

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Mapping Canonical Wnt Signaling in the Developing and Adult Retina

Cited by 97 publications

References 86 publications

Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia

Identification of myopia-associated WNT7B polymorphisms provides insights into the mechanism underlying the development of myopia

Tsukushi functions as a Wnt signaling inhibitor by competing with Wnt2b for binding to transmembrane protein Frizzled4

Bone morphogenetic proteins and secreted frizzled related protein 2 maintain the quiescence of adult mammalian retinal stem cells

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