Activation of Canonical Wnt Pathway Promotes Proliferation of Retinal Stem Cells Derived from Adult Mouse Ciliary Margin

Inoue, Toshihiro; Kagawa, Tetsushi; Fukushima, Mikiko; Shimizu, Takeshi; Yoshinaga, Yutaka; Takada, Shinji; Tanihara, Hidenobu; Taga, Tetsuya

doi:10.1634/stemcells.2005-0124

Cited by 69 publications

(60 citation statements)

References 47 publications

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“…Other recent studies have demonstrated that the modulation of Wnt signaling can affect the numbers of RSCs in developing and adult mouse eyes [31,47], as well as promoting retinal regeneration in adult mammals [48]. In this study, we observed that sFRP2, which binds to Wnt ligands and prevents them from activating their Fzd receptors, specifically blocked the proliferation of RSCs as the numbers but not the sizes of clonal adult RSC spheres were decreased compared to control.…”

Section: Discussionsupporting

confidence: 55%

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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Section: Discussionsupporting

confidence: 55%

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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“…However, their ability to proliferate and generate new retinal neurons, such as photoreceptors, appears to be limited in vivo [33][34] . Mitogens, including basic FGF, insulin, Wnt3a, and pigment epithelium-derived factor, are found to promote the proliferative potential of CE-derived RPCs [35][36][37][38][39] . Transcription factors, such as OTX2, Crx and Chx10, increase the photoreceptor progeny of CE-derived RPCs 40 .…”

Section: Sources Of Endogenous Stem Cells/progenitor Cellsmentioning

confidence: 99%

“…Together, these observations implicate that the nonneurogenic environment of adult mammals may present an inhibitory niche that suppresses the regenerative potential of Müller cells. Similar to Müller cells, CE-derived RSCs have also been found to be capable of re-entering the cell cycle in the presence of certain mitogens, including bFGF, insulin, Wnt3a, and pigment epithelium-derived factor [35][36][37][38][39] . Likely, there is a large overlap in the molecular pathways that regulate the proliferative and regenerative potentials of RPCs of different sources.…”

Section: Niche Signals and Stem Cell Potentialmentioning

confidence: 99%

Mobilizing Endogenous Stem Cells for Retinal Repair

Yu¹,

Talib²,

Vu³

et al. 2016

Translating Regenerative Medicine to the Clinic

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“…Although the number is small in the adult ciliary margin, Wnt3a can increase the self-renewal of retinal stem cells via the canonical pathway (Inoue et al 2006). In addition, a glycogen synthase kinase3 (GSK3) inhibitor mimics the proliferative effect of Wnt3a, which is partly dependent on FGF signaling.…”

Section: Adult Retinal Stem Cellsmentioning

confidence: 99%

Molecular regulation of visual system development: more than meets the eye

Harada¹,

Harada²,

Parada³

2007

Genes Dev.

122

103

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Vertebrate eye development has been an excellent model system to investigate basic concepts of developmental biology ranging from mechanisms of tissue induction to the complex patterning and bidimensional orientation of the highly specialized retina. Recent advances have shed light on the interplay between numerous transcriptional networks and growth factors that are involved in the specific stages of retinogenesis, optic nerve formation, and topographic mapping. In this review, we summarize this recent progress on the molecular mechanisms underlying the development of the eye, visual system, and embryonic tumors that arise in the optic system.For humans, the visual system is a principal conduit for acquiring external sensory information. Thus, "quality of vision" is intimately tied with "quality of life." Despite extensive clinical and laboratory investigation, many diseases that impair vision, ranging from congenital abnormalities to sporadic forms of retinal degeneration, lack effective treatments. One hope is that improved understanding of development of the visual system, from the eye to the visual cortex, will provide insight into methods for attenuating or reversing these disorders. Development of the neural retina and visual system, especially the mechanism of axon remodeling during synaptogenesis, is complex. Studies have shown that numerous genes are involved in the differentiation and formation of the retina acting at specific stages of the development of visual system. In this review, we will summarize recent progress on the molecular mechanisms underlying the development of the eye and visual system. Anatomy of eye developmentThe basic components of the complex optic system are derived from four embryonic sources: forebrain neuroectoderm, intercalating mesoderm, surface ectoderm, and neural crest (Fig. 1). The neuroectoderm differentiates into the retina, iris, and optic nerve; the surface ectoderm gives rise to lens and corneal epithelium; the mesoderm differentiates into the extraocular muscles and the fibrous and vascular coats of the eye; and neural crest cells become the corneal stroma sclera and corneal endothelium. The vertebrate eye originates from bilateral telencephalic optic grooves. In humans, optic vesicles emerge at the end of the fourth week of development and soon thereafter contact the surface ectoderm to induce lens formation. When the lens placode invaginates to form the lens vesicle, the distal part of optic vesicle begins to invaginate to form the optic cup. As the optic vesicles grow, the proximal ends expand and their connections with the forebrain constrict to form optic stalks. Through the retinal fissure, a groove at the inferior aspect of the optic vesicle, the hyaloid artery, enters the eye and nourishes the optic cup and lens vesicle. The retinal fissure normally closes at ∼7 wk of development, and proximal parts of the hyaloid vessels persist to form the central artery and vein of the retina, a branch of the ophthalmic artery. Defects in closure of the fissure result in...

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Activation of Canonical Wnt Pathway Promotes Proliferation of Retinal Stem Cells Derived from Adult Mouse Ciliary Margin

Cited by 69 publications

References 47 publications

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

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

Mobilizing Endogenous Stem Cells for Retinal Repair

Molecular regulation of visual system development: more than meets the eye

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