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Influences on neural lineage and mode of division in the zebrafish retina in vivo.

Poggi L, Vitorino M, Masai I, Harris WA - J. Cell Biol. (2005)

Bottom Line: Proc.Natl.This study provides the first insight into reproducible lineage patterns of retinal progenitors in vivo and the first evidence that environmental signals influence the orientation of cell division and the lineage of neural progenitors.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom.

ABSTRACT
Cell determination in the retina has been under intense investigation since the discovery that retinal progenitors generate clones of apparently random composition (Price, J., D. Turner, and C. Cepko. 1987. Proc. Natl. Acad. Sci. USA. 84:156-160; Holt, C.E., T.W. Bertsch, H.M. Ellis, and W.A. Harris. 1988. Neuron. 1:15-26; Wetts, R., and S.E. Fraser. 1988. Science. 239:1142-1145). Examination of fixed tissue, however, sheds little light on lineage patterns or on the relationship between the orientation of division and cell fate. In this study, three-dimensional time-lapse analyses were used to trace lineages of retinal progenitors expressing green fluorescent protein under the control of the ath5 promoter. Surprisingly, these cells divide just once along the circumferential axis to produce two postmitotic daughters, one of which becomes a retinal ganglion cell (RGC). Interestingly, when these same progenitors are transplanted into a mutant environment lacking RGCs, they often divide along the central-peripheral axis and produce two RGCs. This study provides the first insight into reproducible lineage patterns of retinal progenitors in vivo and the first evidence that environmental signals influence the orientation of cell division and the lineage of neural progenitors.

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More RGCs are generated at the expense of other retinal cell types by ath5:GFP progenitors in the lakritz mutant environment. Increased number of RGCs generated by ath5:GFP progenitors when transplanted in the lakritz environment. (A and B) Longitudinal sections trough the central retina (at 4 d after fertilization) showing ath5:GFP retinal cells (green) in a wild-type environment (A) or in a lakritz mutant environment (B). RGCs are zn-5+ (red), and nuclei have been stained with DAPI to highlight the retinal cell layers. ath5:GFP retinal cells are found mainly in the GCL in a lakritz environment (B), whereas they are distributed in all three layers in the wild-type environment (A). GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer. White dashed lines separate the three retinal layers.
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fig4: More RGCs are generated at the expense of other retinal cell types by ath5:GFP progenitors in the lakritz mutant environment. Increased number of RGCs generated by ath5:GFP progenitors when transplanted in the lakritz environment. (A and B) Longitudinal sections trough the central retina (at 4 d after fertilization) showing ath5:GFP retinal cells (green) in a wild-type environment (A) or in a lakritz mutant environment (B). RGCs are zn-5+ (red), and nuclei have been stained with DAPI to highlight the retinal cell layers. ath5:GFP retinal cells are found mainly in the GCL in a lakritz environment (B), whereas they are distributed in all three layers in the wild-type environment (A). GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer. White dashed lines separate the three retinal layers.

Mentions: Previous in vitro studies suggested that inhibitory feedback signals secreted from differentiated RGCs prevent undifferentiated retinal cells from choosing the RGC fate (Waid and McLoon, 1998; Gonzalez-Hoyuela et al., 2001). If ath5:GFP-positive retinal progenitors respond to such cues, we might expect that the absence of RGCs should change the developmental potential and lineage of these progenitors. We used the lakritz mutant to investigate this question. In lakritz, RGCs fail to differentiate because of a loss of function mutation in the ath5 locus. As a result, the first wave of cells exiting the cell cycle and differentiating as RGCs is missing in lakritz. Instead, the cells that would have differentiated as RGCs appear to stay in the cell cycle for an extra round of division and differentiate into other retinal cell types (Kay et al., 2001). Wondering whether the absence of the inhibitory feedback signals from previously generated RGCs would influence the lineage of wild-type ath5-expressing progenitors, we transplanted blastula-stage cells from ath5:GFP transgenic fish into the blastulas of lakritz mutant host embryos. Fig. 4 shows that there were proportionally more RGCs generated by ath5:GFP cells transplanted to lakritz hosts (∼70%) than there were RGCs generated by the same progenitors transplanted to wild-type embryos (∼40%). The proportion of other ath5:GFP-positive cell types was concomitantly lower (Fig. 4 and see Fig. 6). These data suggest that the lack of RGCs in lakritz hosts indeed biases the developmental behavior of the ath5-expressing progenitors toward an RGC fate.


Influences on neural lineage and mode of division in the zebrafish retina in vivo.

Poggi L, Vitorino M, Masai I, Harris WA - J. Cell Biol. (2005)

More RGCs are generated at the expense of other retinal cell types by ath5:GFP progenitors in the lakritz mutant environment. Increased number of RGCs generated by ath5:GFP progenitors when transplanted in the lakritz environment. (A and B) Longitudinal sections trough the central retina (at 4 d after fertilization) showing ath5:GFP retinal cells (green) in a wild-type environment (A) or in a lakritz mutant environment (B). RGCs are zn-5+ (red), and nuclei have been stained with DAPI to highlight the retinal cell layers. ath5:GFP retinal cells are found mainly in the GCL in a lakritz environment (B), whereas they are distributed in all three layers in the wild-type environment (A). GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer. White dashed lines separate the three retinal layers.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171316&req=5

fig4: More RGCs are generated at the expense of other retinal cell types by ath5:GFP progenitors in the lakritz mutant environment. Increased number of RGCs generated by ath5:GFP progenitors when transplanted in the lakritz environment. (A and B) Longitudinal sections trough the central retina (at 4 d after fertilization) showing ath5:GFP retinal cells (green) in a wild-type environment (A) or in a lakritz mutant environment (B). RGCs are zn-5+ (red), and nuclei have been stained with DAPI to highlight the retinal cell layers. ath5:GFP retinal cells are found mainly in the GCL in a lakritz environment (B), whereas they are distributed in all three layers in the wild-type environment (A). GCL, ganglion cell layer; INL, inner nuclear layer; ONL, outer nuclear layer. White dashed lines separate the three retinal layers.
Mentions: Previous in vitro studies suggested that inhibitory feedback signals secreted from differentiated RGCs prevent undifferentiated retinal cells from choosing the RGC fate (Waid and McLoon, 1998; Gonzalez-Hoyuela et al., 2001). If ath5:GFP-positive retinal progenitors respond to such cues, we might expect that the absence of RGCs should change the developmental potential and lineage of these progenitors. We used the lakritz mutant to investigate this question. In lakritz, RGCs fail to differentiate because of a loss of function mutation in the ath5 locus. As a result, the first wave of cells exiting the cell cycle and differentiating as RGCs is missing in lakritz. Instead, the cells that would have differentiated as RGCs appear to stay in the cell cycle for an extra round of division and differentiate into other retinal cell types (Kay et al., 2001). Wondering whether the absence of the inhibitory feedback signals from previously generated RGCs would influence the lineage of wild-type ath5-expressing progenitors, we transplanted blastula-stage cells from ath5:GFP transgenic fish into the blastulas of lakritz mutant host embryos. Fig. 4 shows that there were proportionally more RGCs generated by ath5:GFP cells transplanted to lakritz hosts (∼70%) than there were RGCs generated by the same progenitors transplanted to wild-type embryos (∼40%). The proportion of other ath5:GFP-positive cell types was concomitantly lower (Fig. 4 and see Fig. 6). These data suggest that the lack of RGCs in lakritz hosts indeed biases the developmental behavior of the ath5-expressing progenitors toward an RGC fate.

Bottom Line: Proc.Natl.This study provides the first insight into reproducible lineage patterns of retinal progenitors in vivo and the first evidence that environmental signals influence the orientation of cell division and the lineage of neural progenitors.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, University of Cambridge, Cambridge CB2 3DY, United Kingdom.

ABSTRACT
Cell determination in the retina has been under intense investigation since the discovery that retinal progenitors generate clones of apparently random composition (Price, J., D. Turner, and C. Cepko. 1987. Proc. Natl. Acad. Sci. USA. 84:156-160; Holt, C.E., T.W. Bertsch, H.M. Ellis, and W.A. Harris. 1988. Neuron. 1:15-26; Wetts, R., and S.E. Fraser. 1988. Science. 239:1142-1145). Examination of fixed tissue, however, sheds little light on lineage patterns or on the relationship between the orientation of division and cell fate. In this study, three-dimensional time-lapse analyses were used to trace lineages of retinal progenitors expressing green fluorescent protein under the control of the ath5 promoter. Surprisingly, these cells divide just once along the circumferential axis to produce two postmitotic daughters, one of which becomes a retinal ganglion cell (RGC). Interestingly, when these same progenitors are transplanted into a mutant environment lacking RGCs, they often divide along the central-peripheral axis and produce two RGCs. This study provides the first insight into reproducible lineage patterns of retinal progenitors in vivo and the first evidence that environmental signals influence the orientation of cell division and the lineage of neural progenitors.

Show MeSH
Related in: MedlinePlus