Cell cycle regulation by trophic factors in Muller stem cells

INSUA F., GARELLI A., ROTSTEIN N. AND POLITI L.

Pinamar, Bs. As., Argentina

Congreso; Reunión conjunta de PABMB, SAIB y SAN; 2005

PABMB, SAIB, SAN

 CELL CYCLE REGULATION BY TROPHIC FACTORS IN MULLER STEM CELLS Insua, Fernanda; Garelli, Andres; Rotstein, Nora and Politi Luis. INIBIBB (UNS-CONICET) CC857 B8000FWB – Bahía Blanca, Argentina. E-mail: mfinsua@criba.edu.ar  Muller glial cells are eye stem cells and hence potentially able to regenerate the different neuronal cell types in the retina. However, their use for this purpose demands to understand the molecular signals that regulate their exit and/or reentry to the cell cycle, and the mechanisms that regulate differentiation into the different neuronal cell types occurring in the retina. We have previously shown that glial derived neurotrophic factor (GDNF) promoted cell cycle progression in Muller cells. We show here that several trophic factors could regulate cell cycle exit and re-entry. In addition to GDNF, basic fibroblast growth factor (bFGF) and insulin stimulated BrdU incorporation and promoted the expression of nestin, a marker of stem and proliferating cells in the retina, and Pax6, a master gene essential for eye development and, hence, probably required during regenerative processes of the retina. In close correspondence with the above results, these trophic factors down regulated the expression of p27, a cell cycle inhibitor. On the contrary, the lipid molecule docosahexaenoic acid (DHA) promoted cell cycle exit of glial cells, diminishing BrdU incorporation, and enhancing p27 expression. As a whole these results suggest that trophic factors regulate the exit or reentry to the cell cycle in Muller stem cells.