EphA4 activity stimulates retinal stem cells proliferation and regulates their sorting in vitro.

OLMOS CARREÑO, CINDY; FIORE, LUCIANO; SCARAFIA, MARÍA AGUSTINA; MAHECHA CASTAÑEDA; JUAN GUILLERMO; SADER LIMA, LUANA; CARRI, NÉSTOR GABRIEL; SANCHEZ, VIVIANA; SCICOLONE, GABRIEL

Mar del Plata

Congreso; XXX SAN Annual Meeting; 2015

Sociedad Argentina de Investigación en Neurociencias

EphA4 activity stimulates retinal stem cells proliferation and regulates their sorting in vitro. Olmos Carreño C1., Fiore L1., Scarafia MA1., Mahecha Castañeda JG1., Sader Lima L1., Carri N2., Sanchez V1., Scicolone G1. (1IBCN; 2 IMBICE).The chicken embryonic retina presents multipotent stem cells in the ciliary zone (CZ). We showed that stem cells express molecules of the Eph-ephrin system. We investigated whether the EphA4 expressed in retinal neurospheres regulates proliferation of stem cells obtained from CZ and whether these stem cells express positional information. We cultured dissociated cells obtained from chicken embryonic nasal and temporal CZ, favoring neurospheres formation. We added BrdU to detect proliferating cells and compared nasal and temporal control neurospheres with nasal and temporal neurospheres treated with Kyl peptide (specific inhibitor of EphA4).We compared the distribution of BrdU + cells, the ratio of BrdU + cells /Hoechst + nucleous, the level of activated EphA4 and the expression of topographic markers (FoxG1 and ephin-A5 for nasal retina). It was shown that: 1) BrdU + cells concentrate in the peripheral zone of neurospheres; 2) partial inhibition of EphA4 activity reduces the proportion of proliferating cells by reducing its density in the peripheral zone, changing their peripheral location to a more homogeneous distribution. 3) It was also shown that nasal neurospheres express higher levels of FoxG1 and ephrin-A5 such as the case for nasal retina. Results show that EphA4 activity not only increases stem cells proliferation but also favors sorting of proliferating cells. Besides, they show that stem cells express positional information. Supported by UBA and CONICET.