Docosahexaenoic Acid Promotes Photoreceptor Differentiation without Altering Crx Expression

Garelli, Andrés; Rotstein, Nora P.; Politi, Luis E.

doi:10.1167/iovs.05-1659

Cited by 42 publications

(58 citation statements)

References 52 publications

(79 reference statements)

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“…In a human placental choriocarcinoma cell line, BeWo cells for instance, RXR antagonists PA451 and HX531 inhibited DHA induction of adipose differentiation-related protein ( Adrp ) mRNA and ADRP protein accumulation ( 44 ), suggesting that DHA activated RXRs to increase ADRP levels. We have previously demonstrated that DHA activates defense mechanisms to prevent apoptosis induced both by oxidative stress and the absence of trophic factors at early stages of development and turns on a program to advance differentiation of photoreceptors ( 54 ). Our present fi ndings demonstrate that DHA requires the activation of RXRs to promote the survival of photoreceptors.…”

Section: Trk Receptors Were Not Involved In the Protective Effect Of Dhasupporting

confidence: 63%

Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors

German

Monaco

Agnolazza

et al. 2013

Journal of Lipid Research

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Section: Trk Receptors Were Not Involved In the Protective Effect Of Dhasupporting

confidence: 63%

Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors

German

Monaco

Agnolazza

et al. 2013

Journal of Lipid Research

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“…Expression peaks at P5, correlating with the onset of rod photoreceptor maturation when rodspecific gene expression is turned up. BrdU incorporation assays confirmed that Crx expressing cells are post-mitotic photoreceptor precursors derived from those cells that have just exited the cell cycle and express Otx2 but not Pax6 (Garelli et al, 2006). Crx is the earliest expressed photoreceptor marker in the retina.…”

Section: 12mentioning

confidence: 76%

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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“…5J-KЈ). This reduction did not reflect a complete loss of the photoreceptor lineage, as Crxpositive postmitotic photoreceptor precursors (Garelli et al, 2006) were still observed (see Fig. S4E,F in the supplementary material).…”

Section: Research Articlementioning

confidence: 94%

Proper differentiation of photoreceptors and amacrine cells depends on a regulatory loop between NeuroD and Six6

et al. 2010

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SUMMARYTimely generation of distinct neural cell types in appropriate numbers is fundamental for the generation of a functional retina. In vertebrates, the transcription factor Six6 is initially expressed in multipotent retina progenitors and then becomes restricted to differentiated retinal ganglion and amacrine cells. How Six6 expression in the retina is controlled and what are its precise functions are still unclear. To address this issue, we used bioinformatic searches and transgenic approaches in medaka fish (Oryzias latipes) to characterise highly conserved regulatory enhancers responsible for Six6 expression. One of the enhancers drove gene expression in the differentiating and adult retina. A search for transcription factor binding sites, together with luciferase, ChIP assays and gain-of-function studies, indicated that NeuroD, a bHLH transcription factor, directly binds an 'E-box' sequence present in this enhancer and specifically regulates Six6 expression in the retina. NeuroD-induced Six6 overexpression in medaka embryos promoted unorganized retinal progenitor proliferation and, most notably, impaired photoreceptor differentiation, with no apparent changes in other retinal cell types. Conversely, Six6 gain-and loss-of-function changed NeuroD expression levels and altered the expression of the photoreceptor differentiation marker Rhodopsin. In addition, knockdown of Six6 interfered with amacrine cell generation. Together, these results indicate that Six6 and NeuroD control the expression of each other and their functions coordinate amacrine cell generation and photoreceptor terminal differentiation.

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Docosahexaenoic Acid Promotes Photoreceptor Differentiation without Altering Crx Expression

Cited by 42 publications

References 52 publications

Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors

Retinoid X receptor activation is essential for docosahexaenoic acid protection of retina photoreceptors

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

Proper differentiation of photoreceptors and amacrine cells depends on a regulatory loop between NeuroD and Six6

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