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Zebrafish Müller glia-derived progenitors are multipotent, exhibit proliferative biases and regenerate excess neurons.

Powell C, Cornblath E, Elsaeidi F, Wan J, Goldman D - Sci Rep (2016)

Bottom Line: Our data indicate that regardless of which nuclear layer was damaged, MG respond by generating multipotent progenitors that migrate to all nuclear layers and differentiate into layer-specific cell types, suggesting that MG-derived progenitors in the injured retina are intrinsically multipotent.However, our analysis of progenitor proliferation reveals a proliferative advantage in nuclear layers where neurons were ablated.This suggests that feedback inhibition from surviving neurons may skew neuronal regeneration towards ablated cell types.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Behavioral Neuroscience Institute, Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109 USA.

ABSTRACT
Unlike mammals, zebrafish can regenerate a damaged retina. Key to this regenerative response are Müller glia (MG) that respond to injury by reprogramming and adopting retinal stem cell properties. These reprogrammed MG divide to produce a proliferating population of retinal progenitors that migrate to areas of retinal damage and regenerate lost neurons. Previous studies have suggested that MG-derived progenitors may be biased to produce that are lost with injury. Here we investigated MG multipotency using injury paradigms that target different retinal nuclear layers for cell ablation. Our data indicate that regardless of which nuclear layer was damaged, MG respond by generating multipotent progenitors that migrate to all nuclear layers and differentiate into layer-specific cell types, suggesting that MG-derived progenitors in the injured retina are intrinsically multipotent. However, our analysis of progenitor proliferation reveals a proliferative advantage in nuclear layers where neurons were ablated. This suggests that feedback inhibition from surviving neurons may skew neuronal regeneration towards ablated cell types.

No MeSH data available.


Related in: MedlinePlus

Injury models stimulate MG proliferation by 2 dpi in the INL.(A) Representative confocal images of retinal sections immunostained for BrdU and GS at 2 dpi following needle poke, PA, and NMDA injuries. Fish were given an injection of BrdU intraperitoneally 3 hours before harvest. Scale bar is equal to 50 μm. (B) PBS was injected into the vitreous of eyes whose retinas were uninjured. Fish were then given an injection of BrdU intraperitoneally 3 hours before harvest at 2 days post PBS injection. Shown are representative images of BrdU immunofluorescence in retinal sections. Similar results were obtained when BrdU was injected at 4 days post PBS injection. ONL, outer nuclear layer; INL, inner nuclear layer; GCL, ganglion cell layer; PA, photoablation; GS, glutamine synthetase; dpi, days post injury.
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f2: Injury models stimulate MG proliferation by 2 dpi in the INL.(A) Representative confocal images of retinal sections immunostained for BrdU and GS at 2 dpi following needle poke, PA, and NMDA injuries. Fish were given an injection of BrdU intraperitoneally 3 hours before harvest. Scale bar is equal to 50 μm. (B) PBS was injected into the vitreous of eyes whose retinas were uninjured. Fish were then given an injection of BrdU intraperitoneally 3 hours before harvest at 2 days post PBS injection. Shown are representative images of BrdU immunofluorescence in retinal sections. Similar results were obtained when BrdU was injected at 4 days post PBS injection. ONL, outer nuclear layer; INL, inner nuclear layer; GCL, ganglion cell layer; PA, photoablation; GS, glutamine synthetase; dpi, days post injury.

Mentions: To investigate the early response of MG to the various injury paradigms, fish received an intraperitoneal (IP) injection of BrdU at 2 dpi when MG are just beginning to proliferate37. These fish were sacrificed 3 hours later, and retinal sections were processed for BrdU and glutamine synthetase (GS) immunofluorescence to investigate injury-dependent MG proliferation (Fig. 2A). This analysis showed that all injury paradigms selectively stimulate MG proliferation in the INL. No MG proliferation was detected in control uninjured retinas (Fig. 2B). These results are consistent with previous studies showing that MG respond to retinal injury by dividing and generating a proliferating population of retinal progenitors318192032.


Zebrafish Müller glia-derived progenitors are multipotent, exhibit proliferative biases and regenerate excess neurons.

Powell C, Cornblath E, Elsaeidi F, Wan J, Goldman D - Sci Rep (2016)

Injury models stimulate MG proliferation by 2 dpi in the INL.(A) Representative confocal images of retinal sections immunostained for BrdU and GS at 2 dpi following needle poke, PA, and NMDA injuries. Fish were given an injection of BrdU intraperitoneally 3 hours before harvest. Scale bar is equal to 50 μm. (B) PBS was injected into the vitreous of eyes whose retinas were uninjured. Fish were then given an injection of BrdU intraperitoneally 3 hours before harvest at 2 days post PBS injection. Shown are representative images of BrdU immunofluorescence in retinal sections. Similar results were obtained when BrdU was injected at 4 days post PBS injection. ONL, outer nuclear layer; INL, inner nuclear layer; GCL, ganglion cell layer; PA, photoablation; GS, glutamine synthetase; dpi, days post injury.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4837407&req=5

f2: Injury models stimulate MG proliferation by 2 dpi in the INL.(A) Representative confocal images of retinal sections immunostained for BrdU and GS at 2 dpi following needle poke, PA, and NMDA injuries. Fish were given an injection of BrdU intraperitoneally 3 hours before harvest. Scale bar is equal to 50 μm. (B) PBS was injected into the vitreous of eyes whose retinas were uninjured. Fish were then given an injection of BrdU intraperitoneally 3 hours before harvest at 2 days post PBS injection. Shown are representative images of BrdU immunofluorescence in retinal sections. Similar results were obtained when BrdU was injected at 4 days post PBS injection. ONL, outer nuclear layer; INL, inner nuclear layer; GCL, ganglion cell layer; PA, photoablation; GS, glutamine synthetase; dpi, days post injury.
Mentions: To investigate the early response of MG to the various injury paradigms, fish received an intraperitoneal (IP) injection of BrdU at 2 dpi when MG are just beginning to proliferate37. These fish were sacrificed 3 hours later, and retinal sections were processed for BrdU and glutamine synthetase (GS) immunofluorescence to investigate injury-dependent MG proliferation (Fig. 2A). This analysis showed that all injury paradigms selectively stimulate MG proliferation in the INL. No MG proliferation was detected in control uninjured retinas (Fig. 2B). These results are consistent with previous studies showing that MG respond to retinal injury by dividing and generating a proliferating population of retinal progenitors318192032.

Bottom Line: Our data indicate that regardless of which nuclear layer was damaged, MG respond by generating multipotent progenitors that migrate to all nuclear layers and differentiate into layer-specific cell types, suggesting that MG-derived progenitors in the injured retina are intrinsically multipotent.However, our analysis of progenitor proliferation reveals a proliferative advantage in nuclear layers where neurons were ablated.This suggests that feedback inhibition from surviving neurons may skew neuronal regeneration towards ablated cell types.

View Article: PubMed Central - PubMed

Affiliation: Molecular and Behavioral Neuroscience Institute, Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109 USA.

ABSTRACT
Unlike mammals, zebrafish can regenerate a damaged retina. Key to this regenerative response are Müller glia (MG) that respond to injury by reprogramming and adopting retinal stem cell properties. These reprogrammed MG divide to produce a proliferating population of retinal progenitors that migrate to areas of retinal damage and regenerate lost neurons. Previous studies have suggested that MG-derived progenitors may be biased to produce that are lost with injury. Here we investigated MG multipotency using injury paradigms that target different retinal nuclear layers for cell ablation. Our data indicate that regardless of which nuclear layer was damaged, MG respond by generating multipotent progenitors that migrate to all nuclear layers and differentiate into layer-specific cell types, suggesting that MG-derived progenitors in the injured retina are intrinsically multipotent. However, our analysis of progenitor proliferation reveals a proliferative advantage in nuclear layers where neurons were ablated. This suggests that feedback inhibition from surviving neurons may skew neuronal regeneration towards ablated cell types.

No MeSH data available.


Related in: MedlinePlus