Mechanics of Neuronal Development
Neuronal circuits are the functional building blocks of the nervous system. To date, a majority of the studies have focused on understanding biochemical cues that govern neuronal migration and axonal elongation. The contribution of mechanical forces in these processes remain largely unexplored. The goal is to investigate the role of mechanical forces in the formation of neuronal circuits.
To explore this aspect of development, the study primarily uses the zebrafish olfactory circuit as a model system. Its location beneath the skin of the transparent embryo, makes it compliant to live imaging and mechanical perturbation. Data suggests that during morphogenesis of the olfactory placode, olfactory axons extend through the effect of extrinsic forces that drive the passive displacement of cell bodies away from their axon tips (Breau et al., Nat Comm, 2017). My postdoctoral project focuses on two main lines of research -
Task 1 - Determine role of the forces
Alter the mechanical condition of the embryo with loss of forces experiments (laser ablation at the cell group scale), and observe the outcome on the change in neuronal behavior during the morphogenesis of the developing olfactory circuit via live imaging and image analysis.
Task 2 : Map of the forces
To obtain a real time noninvasive map of the mechanical forces, we have currently developed an innovative approach based on fluorescently labeled oil droplets to incorporate in the extracellular space of the tissue. The droplets are imaged by confocal microscopy and analyzed to get the deformation field.
Laser ablation of olfactory placodal cells in a transgenic zebrafish embryo (unpublished data)
Live imaging of an oil droplet injected into the olfactory placode during morphogenesis (unpublished data)
Heart Regeneration in Zebrafish
Heart disease has become the leading cause of death in the entire western world. When a person has a heart attack, the heart repairs its damaged muscle by forming scar tissue. As a result, the heart never truly goes back to the way it was.
But unlike ours, if a zebrafish's heart is damaged it will completely repair itself, so that form and function is restored. This fish might be able to teach us how to repair your heart if you have a heart attack. The main objective of my PhD Thesis was to identify the cellular & molecular mechanisms regulating zebrafish heart regeneration.
Gangatharan et al, 2015. Realising Heart Regeneration. Current Tissue Engineering 3, 82-92
Gangatharan et al, 2018. Role of mechanical cues in shaping neuronal morphology and connectivity. Biology of the Cell 110(6):125-136