FUNCTIONAL ANALYSIS OF GENES RELATED TO AGING OF THE NERVOUS SYSTEM IN THE PROCESS OF EMBRYONIC NEUROGENESIS

Adult neurogenesis is the process by which new neural cells are generated from a small population of multipotent stem cells located in specific area of the central nervous system (CNS). The age-related incidence of many CNS diseases coincides with a reduced adult neurogenic potential. The regenerative capability and the amount of adult neural stem cells (aNSCs) decline with age contributing to the reduced functionality of the aged brain. Despite the great interest in age related diseases, in Italy alone over-65 people will rise to the 18% value of 2010 to more than 30% in 2050, the molecular factors responsible for age-dependent decay of aNSCs function are almost unknown. The starting point of my work was a list of brain age-regulated genes that has been previously obtained by RNA-Seq and validated by qPCR and in situ hybridization in the aging animal model system Nothobranchius furzeri. Among them, I analysed the expression profile and the function of Mex3A and Znf367 genes, codifying respectively for a RNA binding protein and a transcription factor, in embryonic neurogenesis. Indeed, we envisage that genes controlling age-dependent processes might act in continuity between development, adulthood, and aging. These genes, of unknown function, are expressed in neuroblasts and retinoblasts of zebrafish and Xenopus laevis embryos and in the aNSCs of the short-lived fish N. furzeri. By means of gene gain and loss of function approaches in Xenopus and zebrafish embryos, I obtained preliminary results on the specific function of these genes in regulating the maintenance of a stem cell-like phenotype or differentiated state in the developing CNS. The same genes will be tested to verify their function also in neural stem cells of adult fishes. The identification of genetic mechanisms involved in embryonic and adult neurogenesis represents the first step in defining interventions that can increase neurogenesis in the aged brain and that could lead to improved maintenance and even repair of neuronal function.