Towards understanding the topological structure of the avian left-right organizer

Jonathan Jackson

Axis specification is critical for proper development and function. In contrast to the well-characterized cilia-based left-right (L/R) symmetry breaking mechanism in many organisms, L/R specification in others, including avians, pigs, and cattle, involves a cilia-independent mechanism of chiral cell flow. In avians, anticlockwise cell movement around the L/R organizer (known as Hensen’s node) displaces initially symmetric L/R determinants. While the genetic pathways are well-established, the roles of mechanics and tissue geometry in this developmental process remain unclear. Previous work from our lab using quail embryos has shown this chiral cell flow requires a tissue-scale, dorsoventrally-oriented torque dipole localized at the node, making avian L/R specification a three-dimensional process rather than a result of two-dimensional cell flow in an epithelial sheet. Furthermore, cells at the node flow and ingress beneath the epiblast, making it a stable tissue-scale structure formed of transient cell-scale components. To address the node’s 3D structure and its connection to torque generation and overall stability, we here determine defect structure and winding number of the coarse-grained nematic director field of cell elongation of the tissue in the vicinity of the node. We find that node-adjacent cells twist along their dorsoventral axis, with the basal side leading the apical in the direction of rotation, while cells farther from the node are not noticeably twisted. Together with the requirement of the node to generate torque, these results provide further insight into the basis of chiral cell flow and how mechanics and geometry can be coupled to specify handedness.