IRCM Researchers

Axon guidance and nervous system circuit formation
One of the research unit's goals is to identify the genes involved in axon guidance by Shh and characterize how they function to guide axons. In parallel to these studies, members of the laboratory are using innovative genetic and live imaging approaches to characterize, with high spatio-temporal resolution, the role of axon guidance molecules, including Shh, in neural circuit formation.

Shh signaling and the pediatric brain tumor medulloblastoma
The research team is interested in other aspects of Shh signaling, including mechanisms underlying the reception of the Shh signal. In this regard, members have identified Boc, Cdon, and Gas1 as essential co-receptors for canonical Shh signaling. This breakthrough has fundamental implications for diseases that result from aberrant Shh signaling, including cancers and developmental disorders. Indeed, they have found that inhibition of Boc helps prevent the formation of medulloblastoma, a pediatric brain tumor. This highlights how abnormal regulation of Shh signaling in the cerebellum can lead to medulloblastoma. They have also discovered that evasion of cellular senescence is an important step in medulloblastoma progression. They are currently interested in the understanding what are the molecular and cellular changes that promote medulloblastoma development.

Approach: Cultivating cells or neural primary tissues in vitro
Because of its relative simplicity, this approach led to look at several molecular and cellular aspects of cell proliferation, cell migration and axon guidance both directly and in real time. To do so, members of the team use high-tech microscopy systems that allow living cells or tissues to be cultivated directly under the microscope. With this approach, they can also observe our samples continuously over several days, thus following their development in detail. They have also developed in the laboratory an axon guidance assay that allows us to measure the turning response of axons to defined gradients of guidance cues.

Approach: Mouse genetics as a model for the study of the molecular mechanisms of axon guidance or medulloblastoma formation. 
For axon guidance, the generation of transgenic mice and the conditional knock-outs are particularly useful for the dissection of these mechanisms over time and within specific neural types. The research unit also has mouse models for medulloblastoma.

Approach: Studying the development of neural circuits in vivo in mice with the help of genetically-encoded fluorescent proteins. 
This technique allows to characterize, with a high spatio-temporal resolution, the development of specific populations of neurons as well as their connection and integration to neural circuits.

Approach: Complementing the mouse genetics, we also utilise CRISPR-Cas9 and in utero electroporation to manipulate genes directly in the cerebellum during development. 
To study axon guidance in embryos, members of the team can also manipulate gene expression by electroporation of siRNA into the spinal cord and culturing the embryos ex vivo, in an approach called whole embryo culture.