β-catenin/Wnt signaling controls progenitor fate in the developing and regenerating zebrafish retina View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-08-24

AUTHORS

Jason R Meyers, Lily Hu, Ariel Moses, Kavon Kaboli, Annemarie Papandrea, Pamela A Raymond

ABSTRACT

BackgroundThe 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.ResultsWe 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.Conclusionsβ-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. More... »

PAGES

30

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1749-8104-7-30

DOI

http://dx.doi.org/10.1186/1749-8104-7-30

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1043125218

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22920725


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93 periphery
94 pharmacological manipulation
95 photoreceptor ablation
96 photoreceptors
97 population
98 progenitor fate
99 progenitors
100 proliferation
101 proliferative cells
102 proliferative state
103 radial glia
104 regeneration
105 regenerative proliferation
106 results
107 retina
108 retinal differentiation
109 retinal injury
110 retinal periphery
111 retinal progenitors
112 retinal stem cells
113 rod photoreceptors
114 signals
115 similar effects
116 specific signals
117 state
118 stem cells
119 zebrafish
120 zebrafish retina
121 zone
122 β-catenin
123 β-catenin accumulates
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