β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina
<p>Abstract</p> <p>Background</p> <p>The zebrafish retina maintains two populations of stem cells: first, the germinal zone or ciliary marginal zone (CMZ) contains multipotent retinal progenitors that add cells to the retinal periphery as the fish continue to grow; seco...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2012-08-01
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| Series: | Neural Development |
| Subjects: | |
| Online Access: | http://www.neuraldevelopment.com/content/7/1/30 |
| _version_ | 1818117723258880000 |
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| author | Meyers Jason R Hu Lily Moses Ariel Kaboli Kavon Papandrea Annemarie Raymond Pamela A |
| author_facet | Meyers Jason R Hu Lily Moses Ariel Kaboli Kavon Papandrea Annemarie Raymond Pamela A |
| author_sort | Meyers Jason R |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The zebrafish retina maintains two populations of stem cells: first, the germinal zone or ciliary marginal zone (CMZ) contains multipotent retinal progenitors that add cells to the retinal periphery as the fish continue to grow; second, radial glia (Müller cells) occasionally divide asymmetrically to generate committed progenitors that differentiate into rod photoreceptors, which are added interstitially throughout the retina with growth. Retinal injury stimulates Müller glia to dedifferentiate, re-enter the cell cycle, and generate multipotent retinal progenitors similar to those in the CMZ to replace missing neurons. The specific signals that maintain these two distinct populations of endogenous retinal stem cells are not understood.</p> <p>Results</p> <p>We used genetic and pharmacological manipulation of the β-catenin/Wnt signaling pathway to show that it is required to maintain proliferation in the CMZ and that hyperstimulation of β-catenin/Wnt signaling inhibits normal retinal differentiation and expands the population of proliferative retinal progenitors. To test whether similar effects occur during regeneration, we developed a method for making rapid, selective photoreceptor ablations in larval zebrafish with intense light. We found that dephosphorylated β-catenin accumulates in Müller glia as they re-enter the cell cycle following injury, but not in Müller glia that remain quiescent. Activation of Wnt signaling is required for regenerative proliferation, and hyperstimulation results in loss of Müller glia from the INL as all proliferative cells move into the ONL.</p> <p>Conclusions</p> <p>β-catenin/Wnt signaling is thus required for the maintenance of retinal progenitors during both initial development and lesion-induced regeneration, and is sufficient to prevent differentiation of those progenitors and maintain them in a proliferative state. This suggests that the β-catenin/Wnt cascade is part of the shared molecular circuitry that maintains retinal stem cells for both homeostatic growth and epimorphic regeneration.</p> |
| first_indexed | 2024-12-11T04:42:56Z |
| format | Article |
| id | doaj.art-286c6ed25d2b43f58655e02d2b90db85 |
| institution | Directory Open Access Journal |
| issn | 1749-8104 |
| language | English |
| last_indexed | 2024-12-11T04:42:56Z |
| publishDate | 2012-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Neural Development |
| spelling | doaj.art-286c6ed25d2b43f58655e02d2b90db852022-12-22T01:20:34ZengBMCNeural Development1749-81042012-08-01713010.1186/1749-8104-7-30β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retinaMeyers Jason RHu LilyMoses ArielKaboli KavonPapandrea AnnemarieRaymond Pamela A<p>Abstract</p> <p>Background</p> <p>The zebrafish retina maintains two populations of stem cells: first, the germinal zone or ciliary marginal zone (CMZ) contains multipotent retinal progenitors that add cells to the retinal periphery as the fish continue to grow; second, radial glia (Müller cells) occasionally divide asymmetrically to generate committed progenitors that differentiate into rod photoreceptors, which are added interstitially throughout the retina with growth. Retinal injury stimulates Müller glia to dedifferentiate, re-enter the cell cycle, and generate multipotent retinal progenitors similar to those in the CMZ to replace missing neurons. The specific signals that maintain these two distinct populations of endogenous retinal stem cells are not understood.</p> <p>Results</p> <p>We used genetic and pharmacological manipulation of the β-catenin/Wnt signaling pathway to show that it is required to maintain proliferation in the CMZ and that hyperstimulation of β-catenin/Wnt signaling inhibits normal retinal differentiation and expands the population of proliferative retinal progenitors. To test whether similar effects occur during regeneration, we developed a method for making rapid, selective photoreceptor ablations in larval zebrafish with intense light. We found that dephosphorylated β-catenin accumulates in Müller glia as they re-enter the cell cycle following injury, but not in Müller glia that remain quiescent. Activation of Wnt signaling is required for regenerative proliferation, and hyperstimulation results in loss of Müller glia from the INL as all proliferative cells move into the ONL.</p> <p>Conclusions</p> <p>β-catenin/Wnt signaling is thus required for the maintenance of retinal progenitors during both initial development and lesion-induced regeneration, and is sufficient to prevent differentiation of those progenitors and maintain them in a proliferative state. This suggests that the β-catenin/Wnt cascade is part of the shared molecular circuitry that maintains retinal stem cells for both homeostatic growth and epimorphic regeneration.</p>http://www.neuraldevelopment.com/content/7/1/30β-catenin/Wnt1-azakenpaulloneXAV939RetinaDevelopmentRegenerationProliferationZebrafishCiliary marginal zone |
| spellingShingle | Meyers Jason R Hu Lily Moses Ariel Kaboli Kavon Papandrea Annemarie Raymond Pamela A β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina Neural Development β-catenin/Wnt 1-azakenpaullone XAV939 Retina Development Regeneration Proliferation Zebrafish Ciliary marginal zone |
| title | β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina |
| title_full | β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina |
| title_fullStr | β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina |
| title_full_unstemmed | β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina |
| title_short | β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina |
| title_sort | β catenin wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina |
| topic | β-catenin/Wnt 1-azakenpaullone XAV939 Retina Development Regeneration Proliferation Zebrafish Ciliary marginal zone |
| url | http://www.neuraldevelopment.com/content/7/1/30 |
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