Neural regeneration in the chick retina

Fischer, Andy J.

doi:10.1016/j.preteyeres.2004.07.003

Cited by 105 publications

(119 citation statements)

References 157 publications

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“…Following NMDA-induced damage, the MGPCs enter S-phase of the cell cycle in synchrony at 2 days after treatment, thereby enabling effective BrdU labeling of the MGPCs and their progeny (Fischer and Reh, 2001). In the chick retina, MGPC proliferation is prominent in peripheral regions of the retina, where the Müller glia are believed to be less mature than in central retina (reviewed by Fischer, 2005), and where we find persistent expression of GCR (see Fig. 2A).…”

Section: Activation Of Gcr Signaling Inhibits the Formation Of Mgpcsmentioning

confidence: 59%

“…Dex activates both the GCR dimer and monomer, and does not discriminate between GCR-dependent transcriptional changes and changes in cell signaling pathways. By comparison, CpdA activates only the monomeric form of GCR that interacts with cytoplasmic proteins , 2005. To better characterize whether activated GCR signaling suppresses the formation of MGPCs because of GCR-dependent transcription or GCRdependent protein-protein interactions, CpdA was applied after NMDA treatment (Fig.…”

Section: Activation Of Gcr Signaling Inhibits the Formation Of Mgpcsmentioning

confidence: 99%

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Glucocorticoid receptors in the retina, Müller glia and the formation of Müller glia-derived progenitors

2014

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Identification of the signaling pathways that influence the reprogramming of Müller glia into neurogenic retinal progenitors is key to harnessing the potential of these cells to regenerate the retina. Glucocorticoid receptor (GCR) signaling is commonly associated with anti-inflammatory responses and GCR agonists are widely used to treat inflammatory diseases of the eye, even though the cellular targets and mechanisms of action in the retina are not well understood. We find that signaling through GCR has a significant impact upon the ability of Müller glia to become proliferating Müller glia-derived progenitor cells (MGPCs). The primary amino acid sequence and pattern of GCR expression in the retina is highly conserved across vertebrate species, including chickens, mice, guinea pigs, dogs and humans. In all of these species we find GCR expressed by the Müller glia. In the chick retina, we find that GCR is expressed by progenitors in the circumferential marginal zone (CMZ) and is upregulated by Müller glia in acutely damaged retinas. Activation of GCR signaling inhibits the formation of MGPCs and antagonizes FGF2/MAPK signaling in the Müller glia. By contrast, we find that inhibition of GCR signaling stimulates the formation of proliferating MGPCs in damaged retinas, and enhances the neuronal differentiation while diminishing glial differentiation. Given the conserved expression pattern of GCR in different vertebrate retinas, we propose that the functions and mechanisms of GCR signaling are highly conserved and are mediated through the Müller glia. We conclude that GCR signaling directly inhibits the formation of MGPCs, at least in part, by interfering with FGF2/MAPK signaling.

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Section: Activation Of Gcr Signaling Inhibits the Formation Of Mgpcsmentioning

confidence: 59%

Section: Activation Of Gcr Signaling Inhibits the Formation Of Mgpcsmentioning

confidence: 99%

Glucocorticoid receptors in the retina, Müller glia and the formation of Müller glia-derived progenitors

2014

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“…Müller glial cells may also have progenitor-like regenerative potential after mild injury and trophic factor stimulation (Ooto et al 2004;Fischer 2005). Müller cells are thought to carry out many of the functions provided by radial glia, astrocytes, and oligodendrocytes in the CNS (Harada et al 2000).…”

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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“…Lineage tracing studies in the developing retinal neuroepithelium showed that a common, multipotent retinal progenitor gives rise to all neurons and Müller glia in the vertebrate retina (Turner and Cepko, 1987;Wetts and Fraser, 1988), and the gene expression profiles of Müller glia and mitotic retinal progenitor cells in developing mouse retina substantially overlap (Blackshaw et al, 2004). Several recent reports describe expression of neuronal markers in Müller glia that proliferate after retinal injury in teleost fish (Yurco and Cameron, 2005;Fausett and Goldman, 2006;Raymond et al, 2006;Fimbel et al, 2007), early postnatal chick (Fischer and Reh, 2003;Fischer, 2005), and adult rodents (Ooto et al, 2004;Das et al, 2006). However, no studies to date have examined the question of whether Müller glia might function as neurogenic radial glia in the uninjured, developing retina.…”

Section: Introductionmentioning

confidence: 99%

Late-Stage Neuronal Progenitors in the Retina Are Radial Muller Glia That Function as Retinal Stem Cells

Bernardos

Barthel

Meyers

et al. 2007

Journal of Neuroscience

583

720

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Neuronal progenitors in the mammalian brain derive from radial glia or specialized astrocytes. In developing neural retina, radial glia-like Müller cells are generated late in neurogenesis and are not considered to be neuronal progenitors, but they do proliferate after injury and can express neuronal markers, suggesting a latent neurogenic capacity. To examine the neurogenic capacity of retinal glial cells, we used lineage tracing in transgenic zebrafish with a glial-specific promoter (gfap, for glial fibrillary acid protein) driving green fluorescent protein in differentiated Müller glia. We found that all Müller glia in the zebrafish retina express low levels of the multipotent progenitor marker Pax6 (paired box gene 6), and they proliferate at a low frequency in the intact, uninjured retina. Müller glia-derived progenitors express Crx (cone rod homeobox) and are late retinal progenitors that generate the rod photoreceptor lineage in the postembryonic retina. These Müller glia-derived progenitors also remain competent to produce earlier neuronal lineages, in that they respond to loss of cone photoreceptors by specifically regenerating the missing neurons. We conclude that zebrafish Müller glia function as multipotent retinal stem cells that generate retinal neurons by homeostatic and regenerative developmental mechanisms.

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Neural regeneration in the chick retina

Cited by 105 publications

References 157 publications

Glucocorticoid receptors in the retina, Müller glia and the formation of Müller glia-derived progenitors

Glucocorticoid receptors in the retina, Müller glia and the formation of Müller glia-derived progenitors

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

Late-Stage Neuronal Progenitors in the Retina Are Radial Muller Glia That Function as Retinal Stem Cells

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