title: Purinergic signals regulate daily S-phase cell activity in the ciliary marginal zone of the zebrafish retina.
abstract: Regeneration and growth that occur in the adult teleost retina have been helpful in identifying molecular and cellular mechanisms underlying cell proliferation and differentiation. Here, it is reported that S-phase cell number, in the ciliary marginal zone (CMZ) of the adult zebrafish retina, exhibits day-night variations with a mid-light phase peak. Oscillations persist for 24 h in constant darkness (DD), suggesting control by a circadian component. However, variations in the S-phase nuclei number were rapidly dampened and not present during and after a second day in DD. An ADPβS treatment significantly enhanced S-phase activity at night to mid-light levels, as assessed by in vivo BrdU incorporation in a 2-h interval. Moreover, daylight increase in S-phase cell number was completely abolished when extracellular nucleotide levels or their extracellular hydrolysis by ectonucleoside triphosphate diphosphohydrolases (NTPDases) were significantly disrupted or when a selective antagonist of purinergic P2Y1 receptors was intraocularly injected before BrdU exposure. Extracellular nucleotides and NTPDase action were also important for maintaining nocturnal low levels of S-phase activity in the CMZ. Finally, we showed that mRNAs of NTPDases 1, 2 (3 isoforms), and 3 as well as of P2Y1 receptor are present in the neural retina of zebrafish. NTPDase mRNA expression exhibited a 2-fold increment in light versus dark conditions as assessed by quantitative RT-PCR, whereas P2Y1 receptor mRNA levels did not show significant day-night variations. This study demonstrates a key role for nucleotides, principally ADP as a paracrine signal, as well as for NTPDases, the plasma membrane-bound enzymes that control extracellular nucleotide concentration, for inducing S-phase cell entry in the CMZ-normally associated with retinal growth-throughout the light-dark cycle.
authors: Facultad de Medicina, Universidad de Buenos Aires, Ciudad de Buenos Aires, Argentina.
authors: Maria Jimena
authors: MJ
authors: Ricatti
authors: Ariadna Gabriela
authors: AG
authors: Battista
authors: Maria
authors: M
authors: Zorrilla Zubilete
authors: Maria Paula
authors: MP
authors: Faillace
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001081:Apyrase / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D057906:Circadian Clocks / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000378:metabolism; D006593:Hexokinase / Q000494:pharmacology; D017440:Photoperiod; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D013873:Thionucleotides / Q000494:pharmacology; D015027:Zebrafish
chemical_list: D004791:Enzyme Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D012333:RNA, Messenger; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; C030812:adenosine 5'-O-(2-thiodiphosphate); D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006593:Hexokinase; D011755:Pyrophosphatases; D001081:Apyrase