Article title Injury-induced purinergic signalling molecules upregulate pluripotency gene expression and mitotic activity of progenitor cells in the zebrafish retina

MATÍAS P. MEDRANO, ARIADNA G. BATTISTA, CLAUDIO A. BEJARANO, GRACIELA D. VENERA, RAMÓN O. BERNABEU AND MARIA PAULA FAILLACE

PURINERGIC SIGNALLING

SPRINGER

Lugar: Berlin; Año: 2017

1573-9538

Damage in fish activates retina repair that restores sight. T hepurinergic signalling system serves multiple homeostatic functionsand has been implicated in cell cycle control of progenitor cells inthe developing retina. We examined whether changes in theexpression of purinergic molecules were instrumental in theproliferative phase after injury of adult zebrafish retinas withouabain. P2RY1 messenger RNA (mRNA) increased early afterinjury and showed maximal levels at the time of peak progenitorcell proliferation. Extracellular nucleotides, mainly ADP, regulateP2RY1 transcriptional and protein expression. T he injury-inducedupregulation of P2RY1 is mediated by an autoregulatedmechanism. After injury, the transcriptional expression ofecto-nucleotidases and ecto-AT Pases also increased andecto-AT Pase activity inhibitors decreased Müller glia-derivedprogenitor cell amplification. Inhibition of P2RY1 endogenousactivation prevented progenitor cell proliferation at two intervalsafter injury: one in which progenitor Müller glia mitotically activatesand the second one in which Müller glia-derived progenitor cellsamplify. ADPβS induced the expression of lin28a and ascl1a genesin mature regions of uninjured retinas. T he expression of thesegenes, which regulate multipotent Müller glia reprogramming, wassignificantly inhibited by blocking the endogenous activation ofP2RY1 early after injury. We consistently observed that the numberof glial fibrillary acidic protein-BrdU-positive Müller cells after injurywas larger in the absence than in the presence of the P2RY1antagonist. Ecto-AT Pase activity inhibitors or P2RY1-specificantagonists did not modify apoptotic cell death at the time of peakprogenitor cell proliferation. T he results suggested that ouabaininjury upregulates specific purinergic signals which stimulatesmultipotent progenitor cell response.