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A20: Corticogenesis and Neuronal Specification in a Mouse Model of Megalencephaly

Project leader: Dr. F. Calegari

The last decade has been characterized by several breakthroughs in the field of neuroscience leading to a better understanding of neural stem cells (NSC) contribution to brain development and evolution, and the role of adult neurogenesis in behaviour and disease. However, major controversy has arisen in the field and formal demonstration of the impact of different precursor pools in brain formation and size is yet to be provided.

Moreover, the role of adult NSC in cognitive function and their use in therapy is highly debated because of the lack of systems that would allow the control of NSC activity in vivo. As a major limitation towards achieving these challenging goals, systems are needed that allow the expansion of NSC and the temporal control of their switch to neurogenesis during development, adulthood, and disease. We believe that this limitation can now be overcome by various paradigms of tissue-specific and temporally-controlled overexpression of cdk4/cyclinD1 allowing the generation of mice with increased brain size and/or adult neurogenesis. Paradigms of NSC expansion will be used to investigate tissue formation during development and to better understand the etiology and impact of NSC in developmentally-related cortical malformations including megalencephaly, lissencephaly, and subcortical laminar heterotopia, which are often linked to childhood epilepsy, mental retardation, and other neurological disorders. 

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Funding program:

DFG