Multipotent Precursors Can Give Rise to All Major Cell Types of the Frog Retina

Wetts, Richard; Fraser, Scott E.

doi:10.1126/science.2449732

Cited by 630 publications

(325 citation statements)

References 19 publications

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“…Lineage tracing and birth dating experiments demonstrated that all of the neuronal cell types in the retina are derived from a common multi-potent progenitor cell (Turner and Cepko, 1987;Wetts and Fraser, 1988). For photoreceptor cells, cones are usually born (exit from the mitotic cycle and commit to the photoreceptor lineage) earlier than rods.…”

Section: Introductionmentioning

confidence: 99%

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

2008

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Rod and cone photoreceptors in the mammalian retina are special types of neurons that are responsible for phototransduction, the first step of vision. Development and maintenance of photoreceptors require precisely regulated gene expression. This regulation is mediated by a network of photoreceptor transcription factors centered on Crx, an Otx-like homeodomain transcription factor. The cell type (subtype) specificity of this network is governed by factors that are preferentially expressed by rods or cones or both, including the rod-determining factors neural retina leucine zipper protein (Nrl) and the orphan nuclear receptor Nr2e3; and cone-determining factors, mostly nuclear receptor family members. The best-documented of these include thyroid hormone receptor β2 (Trβ2), retinoid related orphan receptor Rorβ, and retinoid X receptor Rxrγ. The appropriate function of this network also depends on general transcription factors and co-factors that are ubiquitously expressed, such as the Sp zinc finger transcription factors and STAGA coactivator complexes. These cell type-specific and general transcription regulators form complex interactomes; mutations that interfere with any of the interactions can cause photoreceptor development defects or degeneration. In this manuscript, we review recent progress on the roles of various photoreceptor transcription factors and interactions in photoreceptor subtype development. We also provide evidence of auto-, para-, and feedback regulation among these factors at the transcriptional level. These protein-protein and protein-promoter interactions provide precision and specificity in controlling photoreceptor subtype-specific gene expression, development and survival. Understanding these interactions may provide insights to more effective therapeutic interventions for photoreceptor diseases.

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Section: Introductionmentioning

confidence: 99%

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

2008

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“…Recently, several studies have examined cell lineage in the vertebrate central nervous system (CNS) to see whether neuronal and glial cell types originate from a common precursor or from distinct progenitors (Kornack and Rakic 1995;Reid et al 1995;for review, see Luskin 1994). In cortex (Price and Thurlow 1988;Walsh and Cepko 1988), retina ITurner and Cepko 1987;Holt et al 1988;Wetts and Fraser 1988), and optic tectum (Galileo et al 1990), a single precursor cell can give rise to both neurons and glia as well as different types of neurons even at late stages of neurogenesis. These results imply that multipotential precursors persisting throughout CNS development differentiate in response to local cues.…”

Section: [Abstract: Stem Cells; Neurons; Glia]mentioning

confidence: 99%

Single factors direct the differentiation of stem cells from the fetal and adult central nervous system.

Johe

Hazel²,

Müller³

et al. 1996

Genes Dev.

1,074

865

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Identifying the signals that regulate stem cell differentiation is fundamental to understanding cellular diversity in the brain. In this paper we identify factors that act in an instructive fashion to direct the differentiation of multipotential stem cells derived from the embryonic central nervous system (CNS). CNS stem cell clones differentiate to multiple fates: neurons, astrocytes, and oligodendrocytes. The differentiation of cells in a clone is influenced by extracellular signals: Platelet-derived growth factor (PDGF-AA, -AB, and -BB) supports neuronal differentiation. In contrast, ciliary neurotrophic factor and thyroid hormone T3 act instructively on stem cells to generate clones of astrocytes and oligodendrocytes, respectively. Adult stem cells had remarkably similar responses to these growth factors. These results support a simple model in which transient exposure to extrinsic factors acting through known pathways initiates fate decisions by muhipotential CNS stem cells.

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“…A third possibility is that the addition of SHH-N promotes the proliferation of progenitors at an advanced stage of rod photoreceptor commitment. Although vertebrate retinal progenitors are multipotent (Turner and Cepko, 1987;Holt et al, 1988;Wetts and Fraser, 1988), studies have shown heterogeniety in the responses of retinal progenitors to growth factors and cyclic nucleotide analogs (Taylor and Reh, 1990;Lillien and Cepko, 1992). Furthermore, expression of basic helixloop-helix transcription factors such as Mash I and Cash I are differentially expressed in retinal progenitors at mid to late stages of retinal development in the mouse and chick, respectively (Jasoni et al, 1994;Jasoni and Reh, 1996).…”

Section: Hedgehog Proteins Promote Photoreceptor Differentiation In Vmentioning

confidence: 99%

Sonic Hedgehog Promotes Rod Photoreceptor Differentiation in Mammalian Retinal CellsIn Vitro

et al. 1997

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The hedgehog gene family encodes secreted proteins important in many developmental patterning events in both vertebrates and invertebrates. In the Drosophila eye disk, hedgehog controls the progression of photoreceptor differentiation in the morphogenetic furrow. To investigate whether hedgehog proteins are also involved in the development of the vertebrate retina at stages of photoreceptor differentiation, we analyzed expression of the three known vertebrate hedgehog genes. We found that Sonic hedgehog and Desert hedgehog are expressed in the developing retina, albeit at very low levels, whereas Indian hedgehog (Ihh) is expressed in the developing and mature retinal pigmented epithelium, beginning at embryonic day 13. To determine whether hedgehog proteins have activities on developing retinal cells, we used an in vitro system in which much of retinal histogenesis is recapitulated. N-terminal recombinant Sonic Hedgehog protein (SHH-N) was added to rat retinal cultures for 3-12 d, and the numbers of retinal cells of various phenotypes were analyzed by immunohistochemistry. We found that SHH-N caused a transient increase in the number of retinal progenitor cells, and a 2-to 10-fold increase in the number of photoreceptors differentiating in the cultures when analyzed with three different photoreceptor-specific antigens. In contrast, the numbers of retinal ganglion cells and amacrine cells were similar to those in control cultures. These results show that Hedgehog proteins can regulate mitogenesis and photoreceptor differentiation in the vertebrate retina, and Ihh is a candidate factor from the pigmented epithelium to promote retinal progenitor proliferation and photoreceptor differentiation.

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Multipotent Precursors Can Give Rise to All Major Cell Types of the Frog Retina

Cited by 630 publications

References 19 publications

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

Regulation of photoreceptor gene expression by Crx-associated transcription factor network

Single factors direct the differentiation of stem cells from the fetal and adult central nervous system.

Sonic Hedgehog Promotes Rod Photoreceptor Differentiation in Mammalian Retinal CellsIn Vitro

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