
Project description
Our research program has two interrelated axes aimed at understanding the cellular and molecular mechanisms of (1) nervous system development, and (2) long-term nervous system protection. For our studies, we use the C. elegans microscopic nematode as a powerful genetic and molecular model. C. elegans has already largely contributed to the decoding the processes of brain development and function, as well as aging processes, and the fundamental mechanisms of these processes are remarkably preserved between C. elegans and humans. For the axis (1) we study the mechanisms ensuring the migration of neurons and their axons through complex environments in order to establish connections of functional neural circuits. In particular, we aim to elucidate the regulation and coordination of guidance signals (e.g. netrin) by proteoglycans with heparan sulfate chains. In addition, once formed, the nervous system must be preserved throughout life, despite growth, maturation, and mechanical stress related to movement. For this axis (2), we work to identify molecules regulating the interactions of neurons with their environment and to elucidate their modes of action to ensure the maintenance of the architecture and neuronal connectivity. The results of our research help to elucidate the cellular and molecular mechanisms involved in neurodevelopment and neuroprotection, which are processes that are affected by many orphan diseases of a neurodevelopmental nature (eg, microvillous inclusions disease / congenital mirror movements, Al-Raqad syndrome) and / or neurodegenerative (eg, some cases of rare schizophrenia). Thus, we provide important information that has the potential to contribute to the development of strategies to diagnose, prevent or reduce the consequences of such orphan diseases. In addition, we have active collaborations to validate our results in murine models, and assist in a transition to the clinic.