Cilia-induced flow in the embryonic node of mice and asymmetric gene expression

Abstract

The body plan of many mammals, including humans, shows a very clear internal left-right (LR) asymmetry. The process of LR symmetry breaking starts with asymmetric fluid flow generated by rotating cilia inside a short-lived embryonic cavity called the node. Although a significant amount of experimental and theoretical research has been conducted on the subject, there is no consensus on how fluid flow leads to asymmetric gene expression. At the moment there are two hypothesised mechanisms: chemosensing and mechanosensing. To contribute to the research being done on this subject we make a numerical model of mouse nodal cilia with which we reproduce the flow field inside the node. We discuss the low Reynolds number hydrodynamics of this system; important features include boundary effects and the flow generated by beads. The cilium itself consists of three interconnected filaments of beads attached to a no-slip boundary. Our model reproduces the key features of nodal flow quite well, despite the reducing assumptions made. We find that the flow generated by two cilia is not strong enough to bend an immotile cilium at the periphery of the node, as the mechanosensing hypothesis suggests. Moreover, the traction force on the surface generated by two cilia seems to be too weak to be noticeable. The fluid flow generated by two cilia does seem to be strong enough to create a chemical gradient inside the node, as the chemosensing hypothesis suggests. We conclude that the chemosensing hypothesis seems more likely to be correct than the mechanosensing hypothesis. However, it could be the case that the actual mechanisms for asymmetric gene expression involves a combination of both hypothesised mechanisms.