Cell lineage analysis reveals multipotent precursors in the ciliary margin of the frog retina

Wetts, Richard; Serbedzija, George N.; Fraser, Scott E.

doi:10.1016/0012-1606(89)90146-2

Cited by 194 publications

(132 citation statements)

References 13 publications

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“…Stem cells at the retinal margin of fish and frogs provide a source of all retinal cell types, which incorporate seamlessly as the eye grows (for review, see Reh and Fischer, 2001). Lineage studies suggest that a slowly dividing more primitive stem cell is located far peripherally and capable of producing all retinal cell types as well as pigmented epithelial cells, and that faster cycling, more fate-restricted progenitor cells are located immediately adjacent to the retinal margin (Wetts et al, 1989). More recent work in the frog eye has directly shown expression of Shh signaling molecules in the CMZ, strongly implicating this signaling system in adult retinal proliferation in amphibians (Perron et al, 2003).…”

Section: The Role Of Ptc In the Cmzmentioning

confidence: 99%

Persistent Progenitors at the Retinal Margin ofptc+/- Mice

Moshiri¹,

Reh²

2004

J. Neurosci.

132

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The hedgehog signaling pathway is a key regulator of neural development, affecting both proliferation and differentiation of neural progenitors. Sonic hedgehog (Shh) is a mitogenic factor for retinal progenitors in vitro. To determine whether this signaling system is important in vivo for regulating retinal progenitor proliferation, we analyzed mice with a single functional allele of the Shh receptor patched ( ptc). We found that ptc؉/؊ mice had increased numbers of neural progenitors at every stage of retinal development that we examined. In addition, these mice had persistent progenitors at the retinal margin for up to 3 months of age, reminiscent of the ciliary marginal zone of lower vertebrates. To test whether the progenitors at the retinal margin of ptc؉/؊ mice could be induced to regenerate retinal neurons in response to damage, we bred ptc؉/؊ mice onto a retinal degeneration background (pro23his rhodopsin transgenic) and labeled newly generated cells with combined immunohistochemistry for bromodeoxyuridine and retinal neuron and photoreceptorspecific markers. We found newly generated neurons and photoreceptors at the retinal margin in ptc؉/؊;pro23his mice. We propose that the Shh pathway may act as a regulator of both prenatal and postnatal retinal growth.

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Section: The Role Of Ptc In the Cmzmentioning

confidence: 99%

Persistent Progenitors at the Retinal Margin ofptc+/- Mice

Moshiri¹,

Reh²

2004

J. Neurosci.

132

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“…When RGC, inner nuclear, and photoreceptor cell layers become distinct, Xath5 expression is downregulated in differentiated neurones, but remains in the ciliary marginal zone (CMZ), where retinoblasts are generated throughout life (Fig. 1H,K,L) (Perron et al, 1998;Wetts et al, 1989). Xbh1 expression in the retina is first detected in the dorsal inner optic cup around stage 26-27, shortly after the onset of Xath5 expression (Fig.…”

Section: Xbh1 Expression In the Retina Follows The Spatiotemporal Wavmentioning

confidence: 99%

The homeobox geneXbh1cooperates with proneural genes to specify ganglion cell fate within theXenopusneural retina

et al. 2004

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Recent studies on vertebrate eye development have focused on the molecular mechanisms of specification of different retinal cell types during development. Only a limited number of genes involved in this process has been identified. In Drosophila, BarH genes are necessary for the correct specification of R1/R6 eye photoreceptors. Vertebrate Bar homologues have been identified and are expressed in vertebrate retinal ganglion cells during differentiation; however, their retinal function has not yet been addressed. In this study, we report on the role of the Xenopus Bar homologue Xbh1 in retinal ganglion cell development and its interaction with the proneural genes Xath5 and Xath3, whose ability to promote ganglion cell fate has been demonstrated. We show that XHB1 plays a crucial role in retinal cell determination, acting as a switch towards ganglion cell fate. Detailed expression analysis, animal cap assays and in vivo lipofection assays, indicate that Xbh1 acts as a late transcriptional repressor downstream of the atonal genes Xath3 and Xath5. However, the action of Xbh1 on ganglion cell development is different and more specific than that of the Xath genes, and accounts for only a part of their activities during retinogenesis.

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“…Fish and amphibians produce new retinal neurons throughout life from a germinal region at the peripheral margin of the retina called the ciliary marginal zone (CMZ), which regulates normal retinal development and contributes to retinal regeneration [1][2][3][4][5]. Furthermore, lineage tracing studies have demonstrated that some CMZ cells can give rise to clones containing all types of retinal neurons and M€ uller glial cells [4,6] emphasizing the existence of bona fide retinal stem cells (RSCs) within this specific area. Since no such extensive proliferative and regenerative capacities have been observed in mammals (beyond the postnatal day 10 [PND10] in mice), specifically at the margin of the retina within the ciliary epithelium (CE) [7,8], it was hypothesized that no CMZ per se or bona fide RSCs persist in the adult mammalian eye.…”

Section: Introductionmentioning

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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Cell lineage analysis reveals multipotent precursors in the ciliary margin of the frog retina

Cited by 194 publications

References 13 publications

Persistent Progenitors at the Retinal Margin ofptc+/- Mice

Persistent Progenitors at the Retinal Margin ofptc+/- Mice

The homeobox geneXbh1cooperates with proneural genes to specify ganglion cell fate within theXenopusneural retina

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

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