Impaired brain development in c-fos -/- mice

VELAZQUEZ FN; PRUCCA CG; ETIENNE O; D'ASTOLFO DA; SILVESTRE DC; BOUSSIN F; CAPUTTO BL

Puerto Iguazú

Congreso; 56th International Conference on the Bioscience of lipids; 2015

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 reduction in their body weight and brain size. Consistent with the importance of c-Fos for development is the 40-60% smaller size of c-fos -/- adult mice. Furthermore, only ~40% of c-fos -/- embryos survive until birth and surviving mice live to an average age of 6-7 months, show growth retardation, severe osteopetrosis, delayed or absent gametogenesis, altered haematopoiesis and abnormal behavior, although the development of the Central Nervous System (CNS) of these c-fos -/- mice has not been studied up to date. Early reports showed the need of c-Fos for normal differentiation of cultured PC12 rat cells into sympathetic neuron-like cells and for the regulation of neuronal excitability and survival, among other neuronal functions. Based on these observations and taking into account that several pathologies are related with an impairment in the normal development of the neocortex we studied the importance of c-Fos during CNS development in mice, focusing on the consequence of its lack of expression in the content and fate of NSPCs. We examined the importance of c-Fos during neocortex development at 13.5, 14.5 and 16.5 days of gestation. At E14.5, 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 were analyzed. A ~15% reduction in the neocortex thickness of c-fos-/- embryos was observed which correlates with a decrease