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

CINDY LORENA OLMOS CARREÑO; LUCIANO FIORE; MARIA AGUSTINA SCARAFIA; JUAN GUILLERMO MAHECHA CASTAÑEDA; LUANA SADER LIMA; NÉSTOR G. CARRI; VIVIANA SANCHEZ; GABRIEL SCICOLONE

Mar del Plata

Congreso; XXX Congreso Anual de la Sociedad Argentina de Investigación en Neurosciencias; 2015

Sociedad Argentina de Investigación en Neurociencias

Thechicken embryonic retina presents multipotent stem cells in the ciliary zone(CZ). We showed that stem cells express molecules of the Eph-ephrin system. Weinvestigated whether the EphA4 expressed in retinal neurospheres regulatesproliferation of stem cells obtained from CZ and whether these stem cellsexpress positional information.We cultured dissociated cells obtained from chicken embryonic nasal andtemporal CZ, favoring neurospheres formation. We added BrdU to detectproliferating cells and compared nasal and temporal control neurospheres withnasal and temporal neurospheres treated with Kyl peptide (specific inhibitor ofEphA4).We compared the distribution of BrdU + cells, the ratio of BrdU + cells/Hoechst + nucleous, the level of activated EphA4 and the expression oftopographic markers (FoxG1 and ephin-A5 for nasal retina). It was shown that: 1) BrdU + cells concentrate in the peripheral zone ofneurospheres; 2) partial inhibition of EphA4 activity reduces the proportion ofproliferating cells by reducing its density in the peripheral zone, changingtheir peripheral location to a more homogeneous distribution. 3) It was alsoshown that nasal neurospheres express higher levels of FoxG1 and ephrin-A5 suchas the case for nasal retina. Results show that EphA4 activity not only increases stem cells proliferationbut also favors sorting of proliferating cells. Besides, they show that stemcells express positional information. Supported by UBA and CONICET