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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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Analysis of the orientation of cell division in ath5:GFP progenitors cells. (A) 3D representation of the zebrafish retina as an ellipsoid body (Das et al., 2003). Only divisions where the mitotic spindle is oriented perpendicular to the retinal surface (indicated in yellow and red) can be seen in the zebrafish retina. An example of apico-basal division, which is not found in the zebrafish retina, is also indicated. An orientation of 0° represents a cell division along the central-peripheral (radial) axis, whereas an orientation of 90° represents a division along the circumferential axis (Videos 7 and 8, available at http://www.jcb.org/cgi/content/full/jcb.200509098/DC1). (B) Cumulative distributions of the orientation of cell divisions found in wild-type progenitors when transplanted either into a wild-type host (blue plot) or into lakritz hosts (red plot). The y axis indicates the proportion of cell divisions, whereas the x axis indicates the corresponding angles (n = 20 for both wild-type and lakritz hosts). Divisions that tend to be central-peripheral (<45°) are increased in ath5:GFP progenitors in the lakritz environment. The two distributions differ significantly, as determined by the Kolmogorov-Smirnov test (P = 0.013). (C) Divisions with symmetric outcomes tend to be oriented <45° (radial), whereas divisions with asymmetric outcomes preferentially occur with an angle >45° (circumferential). P = 0.02 by the Chi-squared test; n = 5 in symmetric cases; n = 7 in asymmetric cases.
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fig7: Analysis of the orientation of cell division in ath5:GFP progenitors cells. (A) 3D representation of the zebrafish retina as an ellipsoid body (Das et al., 2003). Only divisions where the mitotic spindle is oriented perpendicular to the retinal surface (indicated in yellow and red) can be seen in the zebrafish retina. An example of apico-basal division, which is not found in the zebrafish retina, is also indicated. An orientation of 0° represents a cell division along the central-peripheral (radial) axis, whereas an orientation of 90° represents a division along the circumferential axis (Videos 7 and 8, available at http://www.jcb.org/cgi/content/full/jcb.200509098/DC1). (B) Cumulative distributions of the orientation of cell divisions found in wild-type progenitors when transplanted either into a wild-type host (blue plot) or into lakritz hosts (red plot). The y axis indicates the proportion of cell divisions, whereas the x axis indicates the corresponding angles (n = 20 for both wild-type and lakritz hosts). Divisions that tend to be central-peripheral (<45°) are increased in ath5:GFP progenitors in the lakritz environment. The two distributions differ significantly, as determined by the Kolmogorov-Smirnov test (P = 0.013). (C) Divisions with symmetric outcomes tend to be oriented <45° (radial), whereas divisions with asymmetric outcomes preferentially occur with an angle >45° (circumferential). P = 0.02 by the Chi-squared test; n = 5 in symmetric cases; n = 7 in asymmetric cases.

Mentions: Apical-basal cell divisions, occurring with the cleavage plane parallel to the retinal surface, have been suggested to be a source of asymmetric cell fates in the vertebrate nervous system (Chenn and McConnell, 1995; Zhong et al., 1996, 1997; Wakamatsu et al., 1999; Cayouette et al., 2001; Cayouette and Raff, 2003). It was previously reported that progenitors in the zebrafish retina do not divide along the apical-basal axis even when they are giving rise to postmitotic daughters (Das et al., 2003). In agreement with this study, we found that all divisions of ath5:GFP cells occurred parallel to the retinal surface (i.e., with the cleavage plane perpendicular to the retinal surface). Interestingly, the same study showed that the proportion of cells dividing in the circumferential axis (>45°) increased over time at the expense of divisions orientated in the central-peripheral or radial axis (<45°; Fig. 7 A and Videos 7 and 8, available at http://www.jcb.org/cgi/content/full/jcb.200509098/DC1). Das et al. (2003) also suggested that the more circumferentially orientated divisions could be asymmetric in nature, whereas the radial divisions could be more symmetric, and showed that the normal shift in orientation was compromised in lakritz mutants. In this study, we show that only 10% of ath5:GFP progenitors transplanted into a wild-type environment divided radially (Fig. 7 B), whereas 45% of these same progenitors transplanted to the lakritz environment divided radially (Fig. 7 B). What is more telling is that we are able, for the first time, to classify asymmetric fate divisions and symmetric fate divisions among normal ath5:GFP-positive progenitors and, thus, to correlate the orientation of division directly with lineage outcome. In asymmetric divisions, one daughter cell became a RGC, whereas the other did not. In symmetric divisions, both daughter cells became RGCs. We found that circumferential divisions tended to give rise to asymmetric or different fates, whereas the radial divisions tended to give rise to symmetric or similar fates (Fig. 7 C).


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)

Analysis of the orientation of cell division in ath5:GFP progenitors cells. (A) 3D representation of the zebrafish retina as an ellipsoid body (Das et al., 2003). Only divisions where the mitotic spindle is oriented perpendicular to the retinal surface (indicated in yellow and red) can be seen in the zebrafish retina. An example of apico-basal division, which is not found in the zebrafish retina, is also indicated. An orientation of 0° represents a cell division along the central-peripheral (radial) axis, whereas an orientation of 90° represents a division along the circumferential axis (Videos 7 and 8, available at http://www.jcb.org/cgi/content/full/jcb.200509098/DC1). (B) Cumulative distributions of the orientation of cell divisions found in wild-type progenitors when transplanted either into a wild-type host (blue plot) or into lakritz hosts (red plot). The y axis indicates the proportion of cell divisions, whereas the x axis indicates the corresponding angles (n = 20 for both wild-type and lakritz hosts). Divisions that tend to be central-peripheral (<45°) are increased in ath5:GFP progenitors in the lakritz environment. The two distributions differ significantly, as determined by the Kolmogorov-Smirnov test (P = 0.013). (C) Divisions with symmetric outcomes tend to be oriented <45° (radial), whereas divisions with asymmetric outcomes preferentially occur with an angle >45° (circumferential). P = 0.02 by the Chi-squared test; n = 5 in symmetric cases; n = 7 in asymmetric cases.
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Related In: Results  -  Collection

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fig7: Analysis of the orientation of cell division in ath5:GFP progenitors cells. (A) 3D representation of the zebrafish retina as an ellipsoid body (Das et al., 2003). Only divisions where the mitotic spindle is oriented perpendicular to the retinal surface (indicated in yellow and red) can be seen in the zebrafish retina. An example of apico-basal division, which is not found in the zebrafish retina, is also indicated. An orientation of 0° represents a cell division along the central-peripheral (radial) axis, whereas an orientation of 90° represents a division along the circumferential axis (Videos 7 and 8, available at http://www.jcb.org/cgi/content/full/jcb.200509098/DC1). (B) Cumulative distributions of the orientation of cell divisions found in wild-type progenitors when transplanted either into a wild-type host (blue plot) or into lakritz hosts (red plot). The y axis indicates the proportion of cell divisions, whereas the x axis indicates the corresponding angles (n = 20 for both wild-type and lakritz hosts). Divisions that tend to be central-peripheral (<45°) are increased in ath5:GFP progenitors in the lakritz environment. The two distributions differ significantly, as determined by the Kolmogorov-Smirnov test (P = 0.013). (C) Divisions with symmetric outcomes tend to be oriented <45° (radial), whereas divisions with asymmetric outcomes preferentially occur with an angle >45° (circumferential). P = 0.02 by the Chi-squared test; n = 5 in symmetric cases; n = 7 in asymmetric cases.
Mentions: Apical-basal cell divisions, occurring with the cleavage plane parallel to the retinal surface, have been suggested to be a source of asymmetric cell fates in the vertebrate nervous system (Chenn and McConnell, 1995; Zhong et al., 1996, 1997; Wakamatsu et al., 1999; Cayouette et al., 2001; Cayouette and Raff, 2003). It was previously reported that progenitors in the zebrafish retina do not divide along the apical-basal axis even when they are giving rise to postmitotic daughters (Das et al., 2003). In agreement with this study, we found that all divisions of ath5:GFP cells occurred parallel to the retinal surface (i.e., with the cleavage plane perpendicular to the retinal surface). Interestingly, the same study showed that the proportion of cells dividing in the circumferential axis (>45°) increased over time at the expense of divisions orientated in the central-peripheral or radial axis (<45°; Fig. 7 A and Videos 7 and 8, available at http://www.jcb.org/cgi/content/full/jcb.200509098/DC1). Das et al. (2003) also suggested that the more circumferentially orientated divisions could be asymmetric in nature, whereas the radial divisions could be more symmetric, and showed that the normal shift in orientation was compromised in lakritz mutants. In this study, we show that only 10% of ath5:GFP progenitors transplanted into a wild-type environment divided radially (Fig. 7 B), whereas 45% of these same progenitors transplanted to the lakritz environment divided radially (Fig. 7 B). What is more telling is that we are able, for the first time, to classify asymmetric fate divisions and symmetric fate divisions among normal ath5:GFP-positive progenitors and, thus, to correlate the orientation of division directly with lineage outcome. In asymmetric divisions, one daughter cell became a RGC, whereas the other did not. In symmetric divisions, both daughter cells became RGCs. We found that circumferential divisions tended to give rise to asymmetric or different fates, whereas the radial divisions tended to give rise to symmetric or similar fates (Fig. 7 C).

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