Functional studies of novel genes in adult neurogenesis in the annual fish Nothobranchius furzeri

• Applicant: Dr. Mario Baumgart
• Subject Area: Developmental Neurobiology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 277624984

Adult neurogenesis is known to decay during ageing.In our previous work, we identified novel genes that are regulate during ageing in the neuronal stem cells.Aim of the present project is to investigate the function of these genes in vivo.To this end, we will use the short-lived fish Nothobranchius furzeri. We selected -based on our prior results- the protein-coding genes MEX3A and ZNF367 based on the following criteria: a) they are expressed and regulated in the aNSC niche, b) their age dependent regulation is conserved in the human brain, and c) they are regulators of gene expression. In addition, we selected miR-15a and the oncomiR-1 cluster as cell-cycle related microRNAs that we previously showed to be specifically regulated upon ageing in the stem cell niche.Aim of the project is to manipulate gene expression in adult neuronal stem cells (aNSCs) in vivo and to measure effects on neurogenesis. We will analyse the following models:1. N. furzeri after acute knock-down of miR-15a 2. N. furzeri after over-expression of oncomiR-1, MEX3A or ZNF367 3. Transgenic N. furzeri And we will quantify changes in adult neurogenesis in response to genetic manipulations.We expect that this project will provide novel insights in the molecular mechanisms that control adult neurogenesis and are responsible for its decay during ageing.

• DFG Programme: Research Grants
• International Connection: Italy
• Cooperation Partners: Professor Dr. Alessandro Cellerino, Ph.D.; Dr. Eva Terzibasi Tozzini