Dr Anne-Gaelle Borycki: Research
Somite and neural tube patterning by Sonic hedgehog signalling
During development, somites form as balls of epithelial cells budding off the pre-somitic mesoderm in an anterior to posterior progression during axis formation. Soon after their formation, somites undergo extensive maturation.
In the ventral somitic domain, cells undergo an epithelial to mesenchymal transition to give rise to the sclerotome, precursor of the cartilage, associated tissues of the vertebrae, and ribs. In the dorsal somitic domain, cells remain epithelial and form the dermomyotome, which will subsequently form the myotome, precursor of body and limb skeletal muscles, and the dermatome, precursor of the skin.
The determination of somitic cells to these distinct fates is tightly regulated during somite formation, such that muscle, dermis and bone progenitors arise at the right time and the right place in the developing vertebrate embryo. For instance, cells from the pre-somitic mesodermare not competent to respond to inductive signals until somites form.
We and others have shown previously that Sonic hedgehog (Shh), a signalling molecule produced by the notochord and the floor plate, plays an essential role in the formation of muscle progenitor cells and sclerotomal progenitor cells. However, the core regulatory processes that coordinate cell fate determination with somite formation depend on the temporal and spatial control of the activation of the downstream components of the Shh signalling pathway, and more specifically the Gli transcription factors that transduce Shh signals.
In my lab, we use an integrative approach, which includes molecular and cellular technologies, transgenic and knockout methodologies in the mouse embryo, and microsurgery and gene expression methodologies in the quail embryo to investigate the transcriptional regulation and function of the Gli genes, mediators of Shh signalling, in cell fate determination during somite development.
