Daily proliferative activity in neurogenic niches of zebrafish retina is regulated by purinergic signals

RICATTI MJ; ARIADNA BATTIST; M. PAULA FAILLACE

Huerta Grande, Córdoba

Congreso; II reunión conjunta de Neurociencias IIRCN - XXV Reunión Anual de la SAN- XII Taller Argentino de Neurociencias; 2010

Sociedad Argentina de Investigación en Neurociencias SAN y Taller de Neurociencias

Growth and regeneration that occur in the adult teleost retina by neurogenesis have been helpful in identifying molecular and cellular mechanisms underlying cell proliferation and differentiation. We have found that cell proliferative activity in a neurogenic area known as the ciliary marginal zone (CMZ) of the adult zebrafish retina follows diurnal variations with highest values observed during the light phase. Proliferative activity in the CMZ did not show circadian variations in constant darkness. ADPβS-treatment significantly enhanced cell division (assessed by BrdU incorporation) at night to normally observed daylight levels. Diurnal increase of proliferation was completely abolished when extracellular nucleotide levels or their extracellular hydrolysis (by ectonucleotidases called NTPDases) were significantly disrupted. Likewise, proliferative activity was inhibited by using an antagonist of purinergic P2Y1 receptors. Finally, we showed that mRNA levels of NTPDases 1, 2 and 3 as well as of P2Y1 receptors are present in the neural retina of zebrafish. NTPDases mRNA expression (by quantitative RT-PCR) exhibited a two-fold increment in light versus dark conditions whereas P2Y1 receptor mRNA levels did not show significant daily variations. Our results demonstrate a key role for nucleotides, mainly ADP as a paracrine signal, as well as for NTPDases for the regulation of the proliferative activity in the CMZ, normally associated with retinal growth, throughout the light:dark cycle.