Fish can regenerate retinal neurons following ocular injury. Evidence
is mounting that astrocytic glia function as inducible, regenerative stem
cells in this process, but the underlying molecular events that enable
neuronal regeneration are comparatively unclear. In the current study gene
array, quantitative real-time PCR, in situ hybridization, and
immunohistochemical approaches were used to identify, in the damaged
retina of adult zebrafish, correlations between transcriptional events and
entry into the cell cycle by Müller cells, a type of astrocytic cell
present in all vertebrate retinas that is a candidate ‘stem
cell’ of regenerated neurons. A proneural gene (achaete-scute
homolog 1a, ash1a) and neurogenic components of the Notch
signaling pathway, including notch3 and deltaA, were
implicated. An injury-induced, enhanced expression of ash1a was
observed in Müller cells, which is hypothesized to contribute to the
transition of these cells, or their cellular progeny, into a
notch3-expressing, regenerative progenitor. A model of vertebrate
retinal repair is suggested in which damage-induced expression of
proneural genes, plus canonical Notch-Delta signaling, could contribute to
retinal stem cell promotion and subsequent regenerative neurogenesis.