The goal of this research proposal is to determine the role of Muller glia and Notch signaling in zebrafish retinal regeneration. Muller cells are a type of radial glia in the retina. Our laboratory has demonstrated that adult fish can regenerate retinal neurons and that Muller glia are mitotically active following retinal damage. What remains unknown are the types of cells produced by proliferating Muller glia in response to retinal injury. Likewise, we do not know the molecular mechanisms responsible for regulating retinal regeneration and retinal stem cell proliferation in the adult zebrafish retina. One candidate is the Notch signaling pathway. Notch has been implicated in regeneration of other zebrafish tissues, suggesting Notch signaling is required for regeneration. We hypothesize that Muller glia function as neuronal stem cells and that Notch signaling is required for activation of the regenerative response. I plan to test this hypothesis by: (1) conducting lineage-tracing experiments to identify the progeny of Muller glia in response to injury; and (2) manipulating Notch signaling in regenerating retinas of adult zebrafish. Understanding the regenerative response of the adult zebrafish retina may bring researches closer to the goal of repairing the effects of retinal damage in people.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Predoctoral Individual National Research Service Award (F31)
Project #
1F31NS047909-01A1
Application #
6883821
Study Section
Special Emphasis Panel (ZRG1-F05 (20))
Program Officer
Owens, David F
Project Start
2005-05-18
Project End
2006-08-17
Budget Start
2005-05-18
Budget End
2006-05-17
Support Year
1
Fiscal Year
2005
Total Cost
$30,432
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Bernardos, Rebecca L; Barthel, Linda K; Meyers, Jason R et al. (2007) Late-stage neuronal progenitors in the retina are radial Muller glia that function as retinal stem cells. J Neurosci 27:7028-40
Raymond, Pamela A; Barthel, Linda K; Bernardos, Rebecca L et al. (2006) Molecular characterization of retinal stem cells and their niches in adult zebrafish. BMC Dev Biol 6:36
Bernardos, Rebecca L; Raymond, Pamela A (2006) GFAP transgenic zebrafish. Gene Expr Patterns 6:1007-13