Crosstalk between signaling pathways for the regulation of neocortical development

The development of the brain from its earliest stages to the complex structures responsible for intricate behaviors involves several critical steps, including proliferation, migration, differentiation, and connectivity formation. Dysregulation of these processes can lead to neurodevelopmental disorders, such as Malformation of Cortical Development, which have significant societal impacts. This thesis focuses on understanding the molecular mechanisms underlying normal and pathological brain development, particularly in the context of RhoA signaling during neocortical neurogenesis. By employing in utero electroporation techniques, the study isolates the effects of RhoA activity on radial glial cells, revealing its roles in proliferation, cell cycle regulation, migration of basal progenitors, and neurogenesis. Additionally, the downstream effector MKL/SRF transcriptional complex and its interaction with Bcl6 were found to be involved in these functions. Furthermore, I participated in an effort to elucidate novel interactions critical for neocortical development, including the interplay between Lgl1 and N-Cadherin in maintaining adherens junctions of neural stem cells, and the relationship between N-Cadherin and Fibroblast Growth Factor Receptors in multipolar neuronal migration. Overall, this research thesis provides insights into the intricate signaling pathways governing brain development, offering potential avenues for therapeutic interventions to address neurodevelopmental disorders and brain injuries.