ROLE OF C-FOS DURING NEUROGENESIS

VELAZQUEZ FN; PRUCCA CG; ETIENNE O; D'ASTOLFO D; SILVESTRE, DO; BOUSSIN FD; CAPUTTO, BL

Rosario

Congreso; 50 Reunion Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2014

c-Fos is a proto-oncogene involved in diverse cellular functions. Its dysregulation has been associated to abnormal development and oncogenic progression. c-fos-/- mice are viable but present a clear reduction in the body weight and size their brain reaches. Herein we examine the importance of c-Fos during development of the neocortex. We studied the cerebral cortex at 14.5 days of gestation (E14.5) (peak of neurogenesis), analyzing neocortex thickness, apoptosis, mitosis and expression of markers along the different stages of Neural Stem Progenitor Cells (NSPCs) differentiation in c-fos-/- and wild-type mice. A ~15% reduction in the neocortex thickness of c-fos-/- embryos was observed which correlates with an increase both in the number of non-differentiated cells (Sox2-positive cells) and the content of apoptotic cells in the ventricular zone. No difference in the rate of mitosis was observed, although the mitotic angle was predominantly vertical in c-fos-/- embryos, suggesting a reduced trend of NSPCs to differentiate. More AP-1/DNA complexes were detected in nuclear extracts of cerebral cortex from c-fos-/- embryos with no differences in the lipid synthesis activity between both groups of embryos. Taken together, these results indicate that c-Fos is involved in the normal development of NSPCs by means of its AP-1 activity.