Centre de Biologie du Développement

Morphogens and Glial specification

Although mechanisms responsible for the formation of neurons and of glial cells, astrocytes and oligodendrocytes, are strictly coordinated and interdependent, the way by which glial cells are recruited remains obscure. Our team is mainly interested by the cellular and molecular aspects of generation of oligodendrocytes, the myelinating cells of the vertebrate central nervous system. In the vertebrate embryonic spinal cord, the time and spatial origin of oligodendrocyte precursors (OLPs) have been well characterized. Our work contributed to point to an important conclusion: OLPs are specified after the onset of neuronal production from ventrally located neural progenitors. We have highlighted the role of Sonic Hedgehog (Shh) in OLP specification by showing that a rise in Shh activity is responsible for the neuronal to oligodendroglial switch of these progenitors. Our main current line of research is aimed at identifying genes involved in triggering this cell fate switch. A differential screen has been performed and genes with restricted or reinforced expression in ventral neural progenitors fated to OLPs have been selected. Among them, we identified Sulfatase 1 (Sulf1), an extracellular 6-0-sulfatase, known to regulate a large number of signaling pathways by modulating interactions of signaling factors with Heparan Sulfate Proteoglycans (HSPGs), major components of the extracellular matrix. Using Drosophila and Chicken, we recently reported that Sulf1 acts as a temporal regulator of Hedgehog/Shh signalling pathway during development. We currently focus on studying Sulf1 function in OLP specification using various vertebrate models (chicken, mouse and zebrafish) and on searching for new players by screening our library enriched in sequences specifically expressed in OLPs at their time of specification.