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P. Yurco, D.A. Cameron; Analysis of Cellular and Molecular Events During Regeneration of Adult Zebrafish Retina . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5746.
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© ARVO (1962-2015); The Authors (2016-present)
Investigate the cellular and molecular events that enable neuronal regeneration in the damaged retina of adult zebrafish.
Gene array, RT–PCR, quantitative real–time PCR, in situ hybridization, and immunohistochemical analyses of control and mechanically lesioned zebrafish retina were performed, 2–35 days post–lesion.
A stereotypical cellular response was observed in extant retina following mechanical injury, including a delayed entry of Müller glia into the cell cycle. The peak of injury–induced cell cycle activity occurred 7 days post–lesion, and extended beyond 600 µm from the lesion site. Consistent with an en place mechanism of lesion–induced regeneration (Yurco & Cameron, Vision Res 45, 991; 2005) longitudinal studies demonstrated that BrdU labeled cells went on to generate new retinal neurons. Gene array analysis of retinal gene expression indicated a complex temporal profile of transcriptional changes, featuring genes related to regenerative phenomena such as clearance of cellular debris, cell cycle progression, axonal growth, and cytogenesis. For several analyzed genes the transcriptional changes displayed a temporal pattern coincident with that of induced cell cycle activity. Gene array, RT–PCR, and quantitative PCR analyses indicated that expression of notch2 and notch3, deltaA and deltaB (Notch receptor ligands), and her4 (a downstream transcription factor), all of which have been implicated in cell fate determination in many systems, were enhanced during the period of cell cycle activity. Furthermore, the expression of achaete scute homolog 1a (ash1a), a proneural bHLH transcription factor and likely target of Notch signaling, was enhanced at the earliest stages of cell cycle activation.
Our results suggest direct correlations between specific cellular and molecular events in damaged retina, and indicate that members of the Notch signaling pathway are targeted for transcriptional regulation in a manner consistent with a hypothesized critical role in enabling retinal regeneration.
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