CONICET PhD fellow
Director: Lucas Sosa
PhD Thesis Topic
The physiological role of the GTPase Rab35 in neuronal migration and in development of the cerebral cortex and its implication in cortical malformation diseases
The development of the cerebral cortex is a complex process that requires an exquisite regulation of multiple cellular events. During the formation of the cerebral cortex, neurons migrate radially from the ventricular and subventricular zone to the cortical plate, simultaneously modifying their morphology and polarity to achieve appropriate migration and connectivity in the central nervous system (CNS). Cell adhesion molecules (CAMs) such as the amyloid precursor protein (APP) and N-cadherin are critical for neurons to carry out these processes. It has been demonstrated that APP expression levels affect neuronal migration and axonal outgrowth. In this context, GTPases play a central role in regulating the traffic of adhesion molecules. Previous studies, in which the function of selected Rab GTPases involved in the endocytic pathway has been altered, showed anomalous membrane expression of adhesion proteins such as cadherin, resulting in aberrant morphology and decrease in neuronal migration in the developing cortex. The Rab35 protein is associated with adhesion proteins and has been reported to participate in neuritogenesis and axonal growth. However, whether Rab35 participates in cortex development through controlling the trafficking of adhesion proteins remains unclear. We propose that the GTPase Rab35 has a critical role in neuronal differentiation and migration during the development of the cerebral cortex by regulating the levels of adhesion proteins APP and N-cadherin.