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Volumn 9, Issue 1, 1999, Pages 37-46

The roles of intrinsic and extrinsic cues and bHLH genes in the determination of retinal cell fates

Author keywords

[No Author keywords available]

Indexed keywords

HELIX LOOP HELIX PROTEIN; NEUROTROPIC AGENT;

EID: 0032965752     PISSN: 09594388     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-4388(99)80005-1     Document Type: Article
Times cited : (290)

References (55)
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    • NeuroD regulates cell fate determination in the developing neural retina
    • Note
    • Morrow EM, Furukawa T, Lee JE, Cepko CL NeuroD regulates cell fate determination in the developing neural retina. Development. 126:1999;23-36. The expression of NeuroD in mouse and rat retina was examined. It was expressed in cells that appeared to be newly postmitotic and fated to be photoreceptors or amacrine cells. Later, expression appeared to be confined to a subset of differentiating amacrine cells; it was then extinguished in mature amacrine cells, but maintained in a subset of photoreceptor cells. The function of NeuroD was studied by forcing expression in developing and mature retinal cells of the rat using a retroviral vector. Several effects were seen: there was a slight reduction in clone size when introduced at P0; there was a complete lack of Müller glia in the marked clones; and there was an increase in amacrine cells and a decrease in bipolar cells. In order to rule out an indirect effect on clonal composition due to forcing cells to prematurely exit the cell cycle, the virus was introduced into the latest stages of development, P4 and P6. At these times, most cells are normally exiting the cell cycle, and the production of Müller glia and bipolar cells is at its peak. The same effects were seen on clone composition as were seen at P0, indicating that these effects were most probably directly on the cell fate choices. Retinal explant cultures were prepared from a NeuroD knockout and examined for effects on the cellular composition. In keeping with the viral misexpression data, there was a fourfold increase in Müller glia, and a twofold increase in the number of bipolar cells. Amacrine differentiation also appeared to have been affected. As Müller glia can divide and may also be more resistant to death in the culture, the change in Müller cell number could have been attributable to proliferation and/or selective survival. Both of these possibilities were examined and disproved. These data indicate that NeuroD has a role in cell fate determination, and most probably plays additional roles in proliferation and differentiation in the retina.
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    • Xath5 participates in a network of bHLH genes in the developing Xenopus retina
    • From Xenopus retina, the authors isolated Xath5, a bHLH gene that is related to the Drosophila atonal gene. Xath5 is expressed in retinal progenitor cells and newly differentiating neurons. It is expressed in some of the same cells as another bHLH gene, NeuroD. Overexpression of Xath5 resulted in an increase in ganglion cells and a decrease in amacrine cells, bipolar cells, and Müller glial cells. Overexpression of NeuroD also resulted in fewer Müller glial cells, but resulted in more bipolar and amacrine cells and had very little effect on ganglion cells. Potential regulatory interactions between these two bHLH genes, and another bHLH gene, Xash3 were explored in the early Xenopus embryo in a primary neurogenesis assay. The authors found that introduction of Xath5 led to broad upregulation of NeuroD, and that introduction of NeuroD led to a more spatially restricted upregulation of Xath5.
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    • Note
    • Perron M, Kanekar S, Vetter ML, Harris WA The genetic sequence of retinal development in the ciliary margin of the Xenopus eye. Dev Biol. 199:1998;185-200. The expression of transcription factors and Notch pathway genes was examined in the Xenopus retina. The authors report the order of expression of genes within cells in the central retina, where differentiation is occurring, and in the ciliary margin zone (CMZ), where the most immature, proliferative cells are located. Co-expression of XNotch-1, X-Delta-1, ESR1, ESR2, Xash3, Xash1, and Xath5 in cells just central to the most immature cells (referred to by the authors as stem cells) of the CMZ was observed. The domain of expression of Xash3 was more narrow, however, ending more peripherally than that of the others, whereas the domain of Xath5, ATH3, and X-MyT1 began more centrally. NeuroD appeared to begin later than the others and to be maintained in the outer portion of the inner nuclear layer (INL) and in the outer nuclear layer (ONL). ATH3 also was maintained in the outer portion of the INL. As predicted by their function in early eye development, XSix3 and Xrx1 were expressed in the most peripheral cells, along with a low level of Pax6, throughout the CMZ, whereas Xotx2 began to be expressed at the same level as NeuroD. Expression of some of these genes in mitotic cells was determined by performing in situ hybridization on BrdU-labeled material. X-Notch-1 and X-Delta-1 were found to be expressed in dividing cells, as shown previously, and Xath5 and NeuroD expression was found to begin in late-stage mitotic cells. Synthesis of all of the above patterns suggests that there is a particular order of expression of these genes, such that four zones of gene expression can be defined. In addition, different combinations of genes appear to be expressed in different layers of the retina: XSix3, Pax6, and Brn 3.0 in the GCL; XSix3, ATH3, Xotx2, NeuroD (and in some cells, Xrx1) in the outer portion of the INL; XSix3, X-MyT1, and Pax6 in the inner portion of the INL; and NeuroD and Xrx1 in the ONL.
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    • •]. Overexpression in the retina using a retroviral vector resulted in an approximately 50% increase in photoreceptor cells, without a concomitant decrease in any other cell population assayed. Infection of cultures of retinal pigmented epithelial cells resulted in an abundance of photoreceptor cells, and no increase in other retinal cell types.
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* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.