Alternating myosin polarity and cell migration during cardiac morphogenesis
Balaghi, Negar 1, 2, 5 ; Fernandez-Gonzalez, Rodrigo 1, 2, 3, 4
1 Institute Of Biomaterials And Biomedical Engineering, University Of Toronto, Toronto, ON, Canada ; 2 Translational Biology And Engineering Program, Ted Rogers Centre For Heart Research, University Of Toronto, ON, Canada ; 3 Cell And Systems Biology, University Of Toronto, Toronto, ON, Canada ; 4 Developmental And Stem Cell Biology Program, Hospital For Sick Kids, Toronto, ON, Canada ; 5 Engineering Science, University Of Toronto, Toronto, ON, Canada
Vertebrate heart development begins with the formation of a primitive heart tube. Contralateral cardiac primordia migrate from opposite sides of the animal and merge medially to form the heart tube. Defective cell migration leads to cardia bifida, a lethal congenital disorder in which the heart tube does not close. In the fruit fly Drosophila melanogaster, the heart is formed from 52 contralateral pairs of cardiac precursors (cardioblasts) that migrate dorsally and medially to join their counterparts. In both vertebrates and invertebrates, heart tube formation is mediated by coordinated cell movements. While the genetic pathways that specify cardiac precursor cell fates are well characterized, little is known about the cellular and molecular mechanisms that govern their migration. Force generation by the actin-based motor myosin II is critical for cell movement. Using live imaging, we investigated the localization and dynamics of myosin during cardioblast migration in living Drosophila embryos. We found that in individual cardioblasts, myosin II displayed an alternating pattern of polarization to the leading and trailing ends of the cells, respectively. We used quantitative image analysis to measure myosin dynamics, and we found that the frequency of oscillation between the leading and trailing edges decreased as heart tube formation progressed and the cells came to a stop. Additionally, myosin oscillations were out of phase between neighbouring cells. Notably, when we visualized myosin in cellular cross-sections, we found that myosin networks also shifted positions between the apical and the basal surface of the cardioblasts, thus inducing rotatory myosin flows within each cell. We are currently investigating the importance of alternating myosin polarity for cardioblast migration, and the role that Rho-family GTPases, well-known regulators of cytoskeletal activity, may play in inducing rotatory myosin flows to drive heart tube morphogenesis.