Immediate differentiation of ganglion cells following mitosis in the developing retina

Waid, David K.; McLoon, Steven C.

doi:10.1016/0896-6273(95)90245-7

Cited by 128 publications

(97 citation statements)

References 41 publications

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“…We present three independent sets of experiments demonstrating that Notch1 transcription is regulated by SOX2; an unbiased ChIP screen identified Notch1 as a direct target of SOX2 in vivo, DNase footprinting and Luciferase reporter assays showed that SOX2 can bind to Notch1 regulatory regions and regulate the levels of NOTCH1 expression in vitro, and finally, both NOTCH1 and its target Hes-5 are dramatically down-regulated in the retinas of Sox2 hypomorphic mice. Furthermore, ablation of NOTCH1 gives a retinal phenotype similar to that which we describe for Sox2-null mice (i.e., loss of RPCs) (Austin et al 1995;Waid and McLoon 1995;Ahmad et al 1997;Henrique et al 1997;Jadhav et al 2006), and the retinal phenotypes of both Hes-1 and Hes-5 mutant mice are strikingly similar to the phenotype observed in Sox2-hypomorphic mice, in that RPCs aberrantly differentiate and abnormal "rosette-like" structures are present (Ishibashi et al 1994;Tomita et al 1996). The lack of balance between lateral inhibitory signaling by NOTCH1 and proneural gene products results in differentiation of RPCs-a mechanism that may extend to other CNS progenitors.…”

Section: Sox2 and Retinal Progenitor Fate Genes And Development 1197mentioning

confidence: 78%

SOX2 is a dose-dependent regulator of retinal neural progenitor competence

Taranova¹,

Magness

Fagan³

et al. 2006

Genes Dev.

506

508

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Approximately 10% of humans with anophthalmia (absent eye) or severe microphthalmia (small eye) show haploid insufficiency due to mutations in SOX2, a SOXB1-HMG box transcription factor. However, at present, the molecular or cellular mechanisms responsible for these conditions are poorly understood. Here, we directly assessed the requirement for SOX2 during eye development by generating a gene-dosage allelic series of Sox2 mutations in the mouse. The Sox2 mutant mice display a range of eye phenotypes consistent with human syndromes and the severity of these phenotypes directly relates to the levels of SOX2 expression found in progenitor cells of the neural retina. Retinal progenitor cells with conditionally ablated Sox2 lose competence to both proliferate and terminally differentiate. In contrast, in Sox2 hypomorphic/null mice, a reduction of SOX2 expression to <40% of normal causes variable microphthalmia as a result of aberrant neural progenitor differentiation. Furthermore, we provide genetic and molecular evidence that SOX2 activity, in a concentration-dependent manner, plays a key role in the regulation of the NOTCH1 signaling pathway in retinal progenitor cells. Collectively, these results show that precise regulation of SOX2 dosage is critical for temporal and spatial regulation of retinal progenitor cell differentiation and provide a cellular and molecular model for understanding how hypomorphic levels of SOX2 cause retinal defects in humans.[Keywords: SOX2; allelic series; retinal progenitor identity; dosage regulation; anopthalmia, microapthalmia] Supplemental material is available at www.genesdev.org. It has recently been shown that mutations in SOX2 a SOXB1-HMG box transcription factor whose expression universally marks neural stem and progenitor cells throughout the CNS including the neural retina (Collignon et al. 1996;Zappone et al. 2000;D'Amour and Gage 2003;Ellis et al. 2004;Ferri et al. 2004), are associated with retinal and ocular malformations in humans. The resulting haploid insufficiency at the SOX2 locus occurs in ∼10% of human individuals with anophthalmia or severe microphthalmia (Fantes et al. 2003;Fitzpatrick and van Heyningen 2005;Hagstrom et al. 2005; Ragge et al. 2005a,b;Zenteno et al. 2005). Most mutations identified to date are point mutations leading to truncations of SOX2, while a smaller class of mutations includes microdeletions and missense point mutations. Interestingly, all mutations produce hypomorphic conditions, where residual SOX2 expression and function are still preserved, albeit at lower levels, leading to the highly variable severity of the clinical phenotype. In this regard, the SOX2 mutations in humans and the clinical consequence of reduced functional levels of SOX2 suggest a dosage-dependent role for SOX2 during retinal progenitor differentiation.To date, the importance of SOX2 in the nervous system has been highlighted by misexpression and domi-

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Section: Sox2 and Retinal Progenitor Fate Genes And Development 1197mentioning

confidence: 78%

SOX2 is a dose-dependent regulator of retinal neural progenitor competence

Taranova¹,

Magness

Fagan³

et al. 2006

Genes Dev.

506

508

View full text Add to dashboard Cite

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“…It is widely accepted that there are axons from ganglion cells in NFL, dendrites from ganglion cells, neurites from amacrine cells, and axons from bipolar cells in IPL, and dendrites from bipolar cells, neurites from horizontal cells, and rod spherules and cone pedicles in OPL. Differentiation of ganglion cells for neuronal outgrowth in developing chicken retina has been shown, by using a ganglion cell-specific antibody (Waid and McLoon, 1995), to begin on E3 and continue to E9, with the peak on ES.…”

Section: Discussionmentioning

confidence: 99%

Transient Expression of PG‐M/Versican, a Large Chondroitin Sulfate Proteoglycan in Developing Chicken Retina

Zako

Shinomura

Miyaishi

et al. 1997

Journal of Neurochemistry

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Abstract:We previously showed the expression of PG-M/versican in embryonic chicken retina. In this study, we characterized the alternatively spliced forms of PG-MI versican and their developmental regulation to investigate the implication of PG-Mlversican in neurite outgrowth from retinal cells during development. On day 5, the immunolocalization of PG-M was first observed at the inner surface of neural retina. On day 7, the pronounced staining was observed in the nerve fiber layer and inner plexiform layer where neural networks of ganglion cells were being formed. As the development proceeded, more intensive staining was observed in these layers. The staining peaked on day 14 and then decreased. Northern analysis and western blotting revealed the presence of a single-sized transcript (13 kb) and the PG-Mlversican core protein (550 kDa) on day 14, but the absence of any transcripts or protein bands on day 20, indicating a transient expression of PG-M + (VO), the alternatively spliced form with the most abundant sites for the chondroitin sulfate attachment. Taken together, it is likely that PG-M/versican is involved in neurite outgrowth from ganglion cells during retinal development, and antiadhesion activity of its chondroitin sulfate chains may be important for regulation. Key Words: PG-M -Versican-Chondroitin sulfate proteoglycan-Neurite outgrowth -Ganglion cell-Retinal development.

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“…Since RA4 labels retinal ganglion cells (Waid & McLoon, 1995) that also express HNK-1/N-CAM (Andressen et al, 1999; our own observation), MAP2 (Tucker & Matus, 1987), and Islet-1 (Austin et al, 1995), we examined whether these markers were expressed in RPE cell cultures treated with bFGF. Monoclonal antibody against Islet-1 stained the nuclei of ganglion cells in the retina (Austin et al, 1995; our own observation) but did not yield immuno-staining signals when applied to the RPE cultures.…”

Section: Bfgf Induced the Expression Of Ra4 Immunogenicitymentioning

confidence: 95%

“…Immunocytochemical staining with monoclonal antibody RA4, which in the retina labels ganglion cells (Waid & McLoon, 1995), detected thousands of positive cells in E6 RPE cultures treated with 25 mg/ml of bFGF ( Fig. 2; Table 1).…”

Section: Bfgf Induced the Expression Of Ra4 Immunogenicitymentioning

confidence: 99%

Differential induction of gene expression by basic fibroblast growth factor and neuroD in cultured retinal pigment epithelial cells

Yan

Wang

2000

Vis Neurosci

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Embryonic chick retinal pigment epithelial (RPE) cells can undergo transdifferentiation upon appropriate stimulation. For example, basic fibroblast growth factor (bFGF) induces intact RPE tissue younger than embryonic day 4.5 (E4.5) to transdifferentiate into a neural retina. NeuroD, a gene encoding a basic helix-loop-helix transcription factor, triggers de novo production of cells that resemble young photoreceptor cells morphologically and express general neuron markers (HNK-1/ N-CAM and MAP2) and a photoreceptor-specific marker (visinin) from cell cultures of dissociated E6 RPE (Yan & Wang, 1998). The present study examined whether bFGF will lead to the same transdifferentiation phenomenon as neuroD when applied to dissociated, cultured E6 RPE cells, and whether interplay exists between the two factors under the culture conditions. Dissociated E6 RPE cells were cultured in the presence or absence of bFGF, and with or without the addition of retrovirus expressing neuroD. Gene expression was analyzed with immunocytochemistry and in situ hybridization. Unlike neuroD, bFGF did not induce the expression of visinin, or HNK-1/N-CAM and MAP2. However, bFGF elicited the expression of RA4 immunogenicity; yet, many of these RA4-positive cells lacked a neuronal morphology. Addition of bFGF to neuroD-expressing cultures did not alter the number of visinin-expressing cells; misexpression of neuroD in bFGF-treated cultures did not change the number of RA4-positive cells, suggesting the absence of interference or synergistic interaction between the two factors. Our data indicated that bFGF and neuroD induced the expression of different genes in cultured RPE cells.

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Immediate differentiation of ganglion cells following mitosis in the developing retina

Cited by 128 publications

References 41 publications

SOX2 is a dose-dependent regulator of retinal neural progenitor competence

SOX2 is a dose-dependent regulator of retinal neural progenitor competence

Transient Expression of PG‐M/Versican, a Large Chondroitin Sulfate Proteoglycan in Developing Chicken Retina

Differential induction of gene expression by basic fibroblast growth factor and neuroD in cultured retinal pigment epithelial cells

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