Julie L. Lefebvre

The research focus of the Lefebvre lab is on developmental neurobiology and neural circuit formation. We investigate how neurons develop and wire up into neural circuits, and seek to identify molecular and cellular mechanisms that guide the formation of these specific connectivity patterns. We also aim to link alterations in neuronal development to abnormal circuit function and behaviour, to better understand how these alterations lead to neurodevelopmental disorders. We use mouse models, molecular-genetic tools to label and manipulate neurons at the population or single-cell level, gene expression profiling, and microscopy. We also develop new methods and apply computational techniques to visualize neuronal wiring and spatially profile neuron type-specific gene expression in intact tissue.

One area of research is the development of GABAergic inhibitory interneurons, which are critical for establishing excitatory-inhibitory balance in the brain. Inhibitory nerve cells are especially vulnerable to early life insults and are implicated in disorders such as epilepsy and autism spectrum disorders. We are studying how diverse types of inhibitory interneurons are generated, and the mechanism that regulates their numbers and wiring patterns in regions such as the retina, cerebellum and cortex.

A second area is the study of cell-surface recognition molecules that mediate selective neuronal interactions to specify wiring and synaptic connectivity. We are especially interested in the clustered Protocadherins (cPcdh), a large family of 58 transmembrane proteins that have a remarkable potential for providing neurons with combinatorial recognition tags. We have shown that the cPcdhs are critical for neuron self/non-self recognition and for inhibitory interneuron development. With new transgenic mouse models and novel methods to study cPcdh diversity in the retina and brain, we are further exploring how the cPcdhs mediate complex patterns of connectivity.

A third area is to study how neuronal connectivity patterns and circuits change in degenerative diseases in the retina that lead to blindness. We have generated new tools to map the wiring patterns following retinal degeneration in mouse models and to track connectivity following manipulations aimed to mitigate or replace degenerating photoreceptors.

Our research is motivated by the goal to better understand how neural circuits develop in the healthy central nervous system, to identify genetic and developmental alterations in circuits that underlie brain disorders, and to advance strategies to restore function.

Courses

• Molecular Genetics Colloquium MMG1010
• Developmental Neurobiology MMG 1301H

Awards

• 2019-2024 Canada Research Chair in Neural Circuit Development, Tier 2 Renewal
• 2014-2019 Canada Research Chair in Neural Circuit Development, Tier 2
• 2015 Sloan Research Fellowship in Neuroscience, Albert P. Sloan Foundation

Cross-affiliations

• Hospital for Sick Children

Look for Dr. Lefebvre on Temerty Medicine Connect