Christopher McFaul and IBBME UofT

February 13, 2020 @ 12:00 pm – 12:30 pm
Red Seminar Room
Donnelly Building

Event Name: Graduate Seminar Series: Cell and Tissue Stream

Graduate Seminar Series for the Institute of Biomaterials and Biomedical Engineering (IBBME). This day is for cell and tissue stream presenters.

Location: Red Seminar Room – Donnelly Building

Presentation Title: Supracellular actin cables and actomyosin-based contraction in Drosophila cardiac morphogenesis.
Abstract: Heart development begins with the formation of a primitive tube, both in fruit flies and mammals. Tube formation is mediated by coordinated cell movements. In the fruit fly Drosophila melanogaster, the heart forms from 52 bi-lateral pairs of cardiac precursors, the cardioblasts, that migrate dorsally and medially to join their counterparts. Pericardial cells connect to the trailing edge of cardioblasts and accompany them in their migration, eventually developing into a haemolymph filtration system. While the genetic pathways that induce cardiac cell fate specification have been clearly defined, the cellular and molecular mechanisms that regulate collective cell migration during heart tube formation are not well understood. Leveraging the simplicity and pharmacological tractability of the fruit fly, and the ability to perform live imaging of its embryos, we have developed a light-sheet microscopy platform and quantitative image analysis to characterize cell behaviours and molecular rearrangements during heart tube formation in living Drosophila embryos. Our system allows identification and tracking of cardiac precursors and the accompanying pericardial cells. Automated image analysis allows quantitative comparison of the dynamics of tube formation across embryos. Using these tools we found that the cytoskeletal protein actin forms a supracellular cable at the interface between cardioblasts and pericardial cells. Laser ablation revealed that the cable sustained tension. Previous work showed that tension-bearing supracellular cables formed by actin and the motor protein myosin II can coordinate cell movements. Consistent with this, we found that myosin pulses transiently integrated into the actin cable. The kinase Rho-kinase (Rok) phosphorylates and activates myosin, and thus inhibiting Rho-kinase results in impaired myosin contractility. Inhibiting Rok and myosin activity by treating embryos with the Rok inhibitor Y-27632 disrupted coordination of cardioblasts in their migration, leading to defects in heart tube formation. Thus, our initial results suggest that Rok may be important for the coordinated movement of cardioblasts during Drosophila heart morphogenesis. Our novel tools will allow us to identify pathways critical for cardiac precursor migration, polarization, and cell-cell adhesion.
Supervisor Name: Rodrigo Fernandez-Gonzalez & Chris Yip
Year of Study: 4
Program of Study: PhD

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