Cell-cell communication in the mammalian nervous system
My laboratory is interested in elucidating the molecular mechanisms by which cells interpret and respond to their environment and how these mechanisms in turn regulate cell fate. We focus more specifically on mechanisms involving direct interaction between neighboring cells in the context of the developing nervous system. Our studies are centred on a distinct cell-cell communication pathway: Eph receptors and their ephrin ligands. We use a variety of approaches to tackle these questions: genetic studies in the mouse, cell biology, biochemistry and global profiling. Our research is divided in two distinct projects:
1. Cell-cell communication in neurogenesis
Neural progenitor cells (NPCs) are self-renewing cells that persist throughout the life of an organism and have the potential to give rise to all cell types in the brain. Studies in vertebrates and invertebrates have highlighted the importance of cell-cell communication for the regulation of maintenance vs. differentiation of NPCs. Indeed, NPCs reside in a special microenvironment formed by different cell types that provide extrinsic cues necessary for their maintenance and differentiation. Recent studies have shown that Eph/ephrin signaling is an important modulator of stem/progenitor cell proliferation and indicate that this communication systems is involved in regulating the switch between proliferation and differentiation in these cells. The aim of our current research is to uncover the molecular mechanisms by which Eph/ephrin signaling might regulate maintenance vs. differentiation of neuroprogenitors and/or neural stem cells.
2. Cell-cell communication in the developing neuromuscular system.
Precursors for motoneurons are born in the ventral spinal cord. Shortly after exiting the cell cycle motoneurons send out axons that grow toward their target muscles. This process is highly regulated as each axon exit the spinal cord in a stereotypical position, navigate through the paraxial mesoderm along a defined route and innervate a pre-determined target muscle. Each of these steps involves pathfinding choices that are based on recognition events. Concomitent with the extension of motor axons is the migration of muscle precursors from the dermomyotomal compartment of somites to the limb bud or other sites of muscle development. Not surprisingly this migration event is also highly regulated both spatially and temporally and some of the molecules that are involved in motor axon pathfinding also serve as guidepost for migrating muscle precursors. Eph receptors and ephrins belong to this family of guidance molecules. The aim of our work is to further understand the mechanisms regulating the development of the neuromuscular system in mammals. We propose to characterize the role of ephrinBs in the development of motoneurons and muscle precursors, and in the innervation of limb muscles. We study two mouse models in which two members of the ephrinB family have been genetically ablated, we have also planned to perform gain-of-function studies in vivo and in vitro in order to identify molecular targets regulated by Eph/ephrinB signaling.
DAVY Alice DR2 CNRS ARVANITIS Dina CR1 CNRS JUNGAS Thomas IE CNRS AUDOUARD Christophe AI CNRS LAUSSU Julien PhD Student
Arvanitis DN, Behar A., Tryoen-Tóth P., Bush J.O., Jungas T., Vitale N. and Davy A. (2013) Ephrin-B1 maintains apical adhesion of neural progenitors. Development. In press. Arvanitis DN and Davy A. (2012) Regulation and mis-regulation of Eph/ephrin expression. Cell Adh Migr. 6: 131-137. Genet G, Guilbeau-Frugier C, Honton B, Dague E, Schneider MD, Coatrieux C, Calise D, Cardin C, Nieto C, Payré B, Dubroca C, Marck P, Heymes C, Dubrac A, Arvanitis DN, Despas F, Altié MF, Seguelas MH, (...)