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Vsx2 in the zebrafish retina: restricted lineages through derepression.

Vitorino M, Jusuf PR, Maurus D, Kimura Y, Higashijima S, Harris WA - Neural Dev (2009)

Bottom Line: Vsx2 is a repressor whose targets include transcription factors such as Vsx1, which is expressed in the progenitors of distinct non-Vsx2 bipolars, and the basic helix-loop-helix transcription factor Ath5, which restricts the fate of progenitors to retinal ganglion cells, horizontal cells, amacrine cells and photoreceptors fates.Foxn4, expressed in the progenitors of amacrine and horizontal cells, is also negatively regulated by Vsx2.Our data thus suggest Vsx2-positive RPCs are fully multipotent retinal progenitors and that when Vsx2 is downregulated, Vsx2-negative progenitors escape Vsx2 repression and so are able to express factors that restrict lineage potential.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK. mspdcv2@cam.ac.uk

ABSTRACT

Background: The neurons in the vertebrate retina arise from multipotent retinal progenitor cells (RPCs). It is not clear, however, which progenitors are multipotent or why they are multipotent.

Results: In this study we show that the homeodomain transcription factor Vsx2 is initially expressed throughout the retinal epithelium, but later it is downregulated in all but a minor population of bipolar cells and all Müller glia. The Vsx2-negative daughters of Vsx2-positive RPCs divide and give rise to all other cell types in the retina. Vsx2 is a repressor whose targets include transcription factors such as Vsx1, which is expressed in the progenitors of distinct non-Vsx2 bipolars, and the basic helix-loop-helix transcription factor Ath5, which restricts the fate of progenitors to retinal ganglion cells, horizontal cells, amacrine cells and photoreceptors fates. Foxn4, expressed in the progenitors of amacrine and horizontal cells, is also negatively regulated by Vsx2.

Conclusion: Our data thus suggest Vsx2-positive RPCs are fully multipotent retinal progenitors and that when Vsx2 is downregulated, Vsx2-negative progenitors escape Vsx2 repression and so are able to express factors that restrict lineage potential.

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Related in: MedlinePlus

Vsx2/Vsx1 down-/upregulation, followed by Vsx2 upregulation. Time-lapse images from Additional file 3 of a double transgenic Tg(vsx1:GFP; vsx2:dsRed) embryo. Vsx2 is initially expressed in the majority of progenitors in the developing neuroepithelium and becomes downregulated in cells that upregulate Vsx1. These cells continue to undergo cell divisions at the apical surface (white arrows) and start differentiating around 40 hours post-fertilization (hpf). Later (around 55 hpf), a subpopulation of cells starts upregulating the expression of Vsx2:DsRed (red arrows) and then differentiates in the inner nuclear layer. Scale bar: 500 μm.
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Figure 6: Vsx2/Vsx1 down-/upregulation, followed by Vsx2 upregulation. Time-lapse images from Additional file 3 of a double transgenic Tg(vsx1:GFP; vsx2:dsRed) embryo. Vsx2 is initially expressed in the majority of progenitors in the developing neuroepithelium and becomes downregulated in cells that upregulate Vsx1. These cells continue to undergo cell divisions at the apical surface (white arrows) and start differentiating around 40 hours post-fertilization (hpf). Later (around 55 hpf), a subpopulation of cells starts upregulating the expression of Vsx2:DsRed (red arrows) and then differentiates in the inner nuclear layer. Scale bar: 500 μm.

Mentions: To investigate how these two bipolar populations are generated, we made time-lapse movies on transgenic embryos. Vsx2-positive bipolar cells were seen to arise from Vsx2-positive progenitors (Figure 2; Additional file 1). After the last division of such a progenitor, Vsx2:GFP expression increases dramatically as the bipolar cells move to their final position in the INL and begin to differentiate. In double transgenic embryos, Tg(vsx2:dsRed;vsx1:GFP), red 'Vsx2-positive' bipolar cells generally arise from progenitors that are 'Vsx1-negative', that is, not green (Figure 5; Additional file 2). Vsx1 expressing bipolar cells, however, initially arise from progenitors that express Vsx2 (Figure 6). However, as soon as Vsx1 expression begins in these progenitors, Vsx2 expression decreases (Figure 6; Additional file 3). Some, and perhaps all, of these Vsx1-positive, Vsx2-negative cells go through at least one round of mitosis before they differentiate (Figures 5 and 6; Additional files 2 and 3). Thus, Vsx2 bipolar cells arise from Vsx2+/Vsx1- progenitors. In contrast, Vsx1-positive progenitors that have downregulated Vsx2 divide to produce Vsx1-positive bipolar cells.


Vsx2 in the zebrafish retina: restricted lineages through derepression.

Vitorino M, Jusuf PR, Maurus D, Kimura Y, Higashijima S, Harris WA - Neural Dev (2009)

Vsx2/Vsx1 down-/upregulation, followed by Vsx2 upregulation. Time-lapse images from Additional file 3 of a double transgenic Tg(vsx1:GFP; vsx2:dsRed) embryo. Vsx2 is initially expressed in the majority of progenitors in the developing neuroepithelium and becomes downregulated in cells that upregulate Vsx1. These cells continue to undergo cell divisions at the apical surface (white arrows) and start differentiating around 40 hours post-fertilization (hpf). Later (around 55 hpf), a subpopulation of cells starts upregulating the expression of Vsx2:DsRed (red arrows) and then differentiates in the inner nuclear layer. Scale bar: 500 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC2683830&req=5

Figure 6: Vsx2/Vsx1 down-/upregulation, followed by Vsx2 upregulation. Time-lapse images from Additional file 3 of a double transgenic Tg(vsx1:GFP; vsx2:dsRed) embryo. Vsx2 is initially expressed in the majority of progenitors in the developing neuroepithelium and becomes downregulated in cells that upregulate Vsx1. These cells continue to undergo cell divisions at the apical surface (white arrows) and start differentiating around 40 hours post-fertilization (hpf). Later (around 55 hpf), a subpopulation of cells starts upregulating the expression of Vsx2:DsRed (red arrows) and then differentiates in the inner nuclear layer. Scale bar: 500 μm.
Mentions: To investigate how these two bipolar populations are generated, we made time-lapse movies on transgenic embryos. Vsx2-positive bipolar cells were seen to arise from Vsx2-positive progenitors (Figure 2; Additional file 1). After the last division of such a progenitor, Vsx2:GFP expression increases dramatically as the bipolar cells move to their final position in the INL and begin to differentiate. In double transgenic embryos, Tg(vsx2:dsRed;vsx1:GFP), red 'Vsx2-positive' bipolar cells generally arise from progenitors that are 'Vsx1-negative', that is, not green (Figure 5; Additional file 2). Vsx1 expressing bipolar cells, however, initially arise from progenitors that express Vsx2 (Figure 6). However, as soon as Vsx1 expression begins in these progenitors, Vsx2 expression decreases (Figure 6; Additional file 3). Some, and perhaps all, of these Vsx1-positive, Vsx2-negative cells go through at least one round of mitosis before they differentiate (Figures 5 and 6; Additional files 2 and 3). Thus, Vsx2 bipolar cells arise from Vsx2+/Vsx1- progenitors. In contrast, Vsx1-positive progenitors that have downregulated Vsx2 divide to produce Vsx1-positive bipolar cells.

Bottom Line: Vsx2 is a repressor whose targets include transcription factors such as Vsx1, which is expressed in the progenitors of distinct non-Vsx2 bipolars, and the basic helix-loop-helix transcription factor Ath5, which restricts the fate of progenitors to retinal ganglion cells, horizontal cells, amacrine cells and photoreceptors fates.Foxn4, expressed in the progenitors of amacrine and horizontal cells, is also negatively regulated by Vsx2.Our data thus suggest Vsx2-positive RPCs are fully multipotent retinal progenitors and that when Vsx2 is downregulated, Vsx2-negative progenitors escape Vsx2 repression and so are able to express factors that restrict lineage potential.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge, CB2 3DY, UK. mspdcv2@cam.ac.uk

ABSTRACT

Background: The neurons in the vertebrate retina arise from multipotent retinal progenitor cells (RPCs). It is not clear, however, which progenitors are multipotent or why they are multipotent.

Results: In this study we show that the homeodomain transcription factor Vsx2 is initially expressed throughout the retinal epithelium, but later it is downregulated in all but a minor population of bipolar cells and all Müller glia. The Vsx2-negative daughters of Vsx2-positive RPCs divide and give rise to all other cell types in the retina. Vsx2 is a repressor whose targets include transcription factors such as Vsx1, which is expressed in the progenitors of distinct non-Vsx2 bipolars, and the basic helix-loop-helix transcription factor Ath5, which restricts the fate of progenitors to retinal ganglion cells, horizontal cells, amacrine cells and photoreceptors fates. Foxn4, expressed in the progenitors of amacrine and horizontal cells, is also negatively regulated by Vsx2.

Conclusion: Our data thus suggest Vsx2-positive RPCs are fully multipotent retinal progenitors and that when Vsx2 is downregulated, Vsx2-negative progenitors escape Vsx2 repression and so are able to express factors that restrict lineage potential.

Show MeSH
Related in: MedlinePlus