Research group Yves-Alain Barde
Molecular mechanisms underlying the development of the nervous system
To understand the cause of diseases of the nervous system we explore the processes controlling the development of neurons in the embryo.
The nervous system consists of functional units called neurons which stop dividing early during development. This is a major reason why the adult nervous system is essentially unable to regenerate after lesion and in neurodegenerative diseases. The lack of cell division also creates a very significant experimental problem as neurons cannot be simply expanded in culture to study them, unlike cells of the immune system or cancer cells.
Our group investigates how growth factors keep neurons alive during development and regulate the function of neuronal networks. Our research focusses on brain-derived neurotrophic factor (BDNF), a molecule known to be essential for a number of processes, including memory in humans. Also, animal models have revealed that its levels are decreased in pathological conditions such as obesity, depression, Huntington’s disease and Rett syndrome. An important goal is then to explore the potential of well-tolerated substances towards increasing BDNF levels over prolonged periods of time. We recently found that the new drug fingolimod introduced for the treatment of multiple sclerosis increases BDNF levels in specific brain areas. It also markedly improves locomotor deficits in mouse models of Rett syndrome (see Deogracias et al., 2012 in Publications).
Like other growth factors, BDNF binds to receptors localized on neurons. The problem resulting from the lack of division of these cells was solved by the development a cell culture method based on embryonic cells. When kept undifferentiated, these cells divide indefinitely, a property that also allows their genome to be engineered in specific ways. Under well-defined conditions, these embryonic stem cells can be differentiated into post-mitotic neurons closely resembling those found in the brain. This system greatly facilitates the understanding of the mode of action of growth factors and of their receptors in neurons. Related studies are also underway using human embryonic stem cells and reprogrammed cells, opening the way to a much better understanding of neuronal dysfunction.