Participation of c-fos in the biology of neural stem cell of the central nervous system

FN VELAZQUEZ; DA D'ASTOLFO; BL CAPUTTO

Paris

Congreso; Advances in Stem Cell Research: Development, Regeneration and Disease.; 2011

Instituto Pasteur

c-Fos, a transcription factor involved in proliferation of normal and tumor cells, also activates phospholipid synthesis. An increased expression of c-Fos in brain tumors promotes growth by increasing the rate of lipid synthesis; in a mouse model of Neurofibromatosis type 1 (NPcis) that spontaneously develop tumors, no tumors develop in the absence of c-Fos. Cancer can be considered a disease of unregulated cell self-renewal in which mutations convert normal pathways of stem cell self renewal into engines for neoplastic proliferation. So, it results important to study stem cell biology and particularly that of c-Fos to understand tumor development. We observed that mice c-fos -/- have three times less neural stem cells in the SVZ than mice c-fos +/+ (% stem cells/total cells: c-fos -/- 0.76%; c-fos +/+ 2.3%). In addition, after 28 days of culture, neural stem/progenitor c-fos -/- cells show less proliferation in TH3 assays (c-fos -/- 13693+-3993 cpm; c-fos +/+ 41073+-2224 cpm) and increased apoptosis as determined by annexin V (c-fos +/+ 1.47%; c-fos -/- 3.05%). EMSA studies showed no changes in AP-1 content in both conditions, with activated synthesis of phospholipids in c-fos +/+ animals. These results evidence that c-Fos is involved in controlling self-renewal of neural stem cells and that it affects the comportment of neural stem/progenitor cells.