uPA promotes retinal progenitors proliferation, neuronal differentiation and retinal ganglion cells axon growth.

MEDORI, MARA; RONDON, JONATHAN; SCICOLONE, GABRIEL; SPELZINI, GONZALO; SANCHEZ, VIVIANA; ROBALDO, MANUEL; FIORE, LUCIANO

Congreso; SAN 2020. XXXV Virtual Meeting; 2020

Sociedad Argentina de Investigacion en Neurociencias

uPA promotes retinal progenitors proliferation, neuronal differentiation and retinal ganglion cells axon growth. MARA MEDORI*1,2; MANUEL ROBALDO1,2; GONZALO SPELZINI1,2; JONATHAN RONDON1,2; LUCIANO FIORE1,2; VIVIANA SANCHEZ1,2; GABRIEL SCICOLONE1,2.1. CONICET ? Universidad de Buenos Aires, Instituto de Biología Celular y Neurociencias ?Prof. E. De Robertis? (IBCN). Ciudad de Buenos Aires, Argentina.2, Universidad de Buenos Aires, Facultad de Medicina, Departamento de Biología Celular, Histología, Embriología y Genética. Ciudad de Buenos Aires, Argentina.Previously we demonstrated that urokinase-type plasminogen activator (uPA) increases neuronal migration and neuritogenesis in chicken tectal neurons. Other reports involved uPA in proliferation processes. The purpose of this work was to evaluate the role of uPA in chicken retinal development. We observed that uPA receptor (uPAR) expresses in developing retina, including the retinal ganglion cells (RGCs) that establish topographic connections with the tectum.In order to investigate whether uPA regulates the level of proliferation of retinal progenitors and neuronal differentiation, we cultured dissociated retinal cells obtained from embryos of 5 days of development (E5) and exposed them to control conditions or uPA. The proportion of cells expressing BrdU and presenting neuronal phenotype were evaluated. Results showed that uPA increases the proportion of BrdU+ cells and projecting neurons. Then we studied the effect of uPA on RGC axon growth in retinal explants obtained from E7 exposed to control conditions or uPA. Results showed that uPA increases RGC axon growth. In order to investigate downstream signaling participating in uPA-mediated axon growth, the level of FAK activity was evaluated by immunocytochemistry and Westernblot. Results showed that uPA increases FAK activity. This work shows that uPA promotes proliferation of retinal progenitors and the level of neuronal differentiation, also increases RGC axon growth by increasing the level of FAK activity. Supported by UBACYT 0769.Key words: urokinase-type plasminogen activator, proliferation, differentiation, axon growth, retinal ganglion cells, retinotectal system, chick embryo, development.