ADAMs are cell-surface-Metalloproteases that contain a Disintegrin domain. They were
initially discovered on the surface of mature spermatozoid where they play a role during
fertilization. The domain organization of ADAM proteins is related to snake venom
metalloproteases. When these venoms are released into a victim, the metalloprotease
domain degrades the walls of blood vessels while the disintegrin domain prevents platelet
integrins from binding and forming blood clots. The combination of these 2 functions
induces hemorrhages that can lead to the death of the victim. My group is interested in
cell movements that shape the vertebrate embryo. More precisely we are interested in cell
interactions either with other cells or with the extracellular environment that control
cell movements. We have chosen the Frog embryo (Xenopus Laevis) to study these phenomena
because of the large number of embryos that can be generated (thousandths per female),
the wide array of molecular reagents available for this specie and the amount of
knowledge accumulated over the years by classical embryologists.
Our current research is centered on the function of the ADAM13 metalloprotease during
cranial neural crest cell migration. Cranial neural crest are cells that originate at the
lateral edge of the anterior neural plate and migrate toward the ventral side of the
embryo to colonize the head and make most of the facial cartilages, muscle and bones of
the face. These cells are present in all vertebrates including humans. We have shown that
if ADAM13 function is prevented, cranial neural crest cells do not migrate into their
normal migration pathways. We also showed that ADAM13 binds, cleaves and remodels a
substrate composed of the extracellular matrix protein fibronectin. Our current model is
that ADAM13 function is to modify the cranial neural crest cell pathways to promote
migration of subpopulation of cells in the correct paths.
Our multiple interests in cell behaviors during embryogenesis are reflected by our wide
array of techniques. We use Molecular Biology to clone, mutate, express or knock-out
genes that we want to study. Biochemical analyzes to identify protein complexes,
proteolytic substrates and post-transcriptional regulation of selected proteins in the
embryos. Finally we use grafts, live labeling and imaging of cells in whole embryos as
well as in vitro cultured explants to understand detail cellular behavior in response to
various conditions.
