ADDUCINS AFFECT CORTICAL NEUROGENESIS BY REGULATING PROGENITORS¿ MORPHOLOGY AND FATE

Human intellectual abilities largely depend on the expansion of the mammalian cerebral cortex, the brain region responsible for cognition, reasoning, language and so much more. Across evolution, neocortex expanded massively, reaching a critical size in human. The main reason for this change can be found during neocortical development in an increased neuronal production during a prolonged neurogenic period. Neocortical development starts during embryogenesis with the main neural progenitor cells, classified as apical (APs) and basal progenitors (BPs). BPs are significantly enriched and highly proliferating in gyrencephalic species compared to lissencephalic, leading to an increased neuronal outcome and to cortical folding. BPs are a highly heterogeneous population: they can be classified in basal intermediate progenitors (bIPs) and basal radial glia (bRG) based on morphology and proliferative capability. It was observed that a higher number of cell processes positively correlates with proliferation. The molecular mechanisms that drive this connection are only partially understood. Structural proteins have already been described as determinants of BPs’ morphology and fate; among them, the family of adducins (ADDs) is of particular interest. ADD1, ADD2 and ADD3 anchor the spectrin-actin cytoskeleton to the cell membrane through their interaction with other transmembrane proteins. They have recently been associated with various neurodevelopmental disorders, such as ventriculomegaly and corpus callosum dysgenesis, suggesting a possible role in the context of neocortical development. My PhD project explored their effect on progenitors’ morphology, proliferation and neuronal outcome, providing further insights into the mechanisms that regulate brain development and expansion.