Cilia: they bend but do not break
Cell Rep March 13, 2014
Feb. 20, 2014
From bacteria to mammals, cell cilia are essential structures for life. However, their role is often poorly understood. Thanks to an innovative imaging technique, the team of Julien Vermot at the IGBMC could visualize in real time the role of endothelial cilia during the development of the vascular system in zebrafish. They measured the forces driving the deformation of cilia in the blood vessels and were able to reconstruct the three-dimensional internal structure of a cilium. In this new study, the researchers show that the cilia of endothelial cells play a central role in the development of the vascular system. This work is published on 20 February 2014 in the journal Cell Reports.
While for many years they hardly attracted the interest of biologists, these long and thin cell surface structures are gradually gaining respectability. Cilia have many essential functions at the organ level and at that of the whole organism. Those present in the nose, for example, are essential for odour perception, while in the inner ear they detect head movements and thus help maintain balance. When defective, numerous health problems can occur; obesity and fertility disorders, muscle, kidney and lung problems have all been associated with the function of cilia. They also play an important role during embryonic development, during which serious consequences can arise when they are deficient, such as a reversed arrangement of the internal organs.
Julien Vermot’s team at the IGBMC focused on the role of cilia in endothelial cells, which form blood vessels, during development. In zebrafish, a few hours after fertilization, most endothelial cells of the circulatory system are ciliated. The researchers demonstrated that the cilia are, in fact, mechanosensors being highly sensitive to tiny variations in the motion of the blood cells circulating in the growing blood vessels. In this environment, they bend in response to the blood flow and the angle of this bending was seen to be proportional to the force of the blood flow. This allows the low blood flow forces generated by the heart, which beats gently at early stages, to be detected by the endothelial cells. While they are absolutely essential to the early development of the vascular system, cilia were seen to disappear as the heart beat grows stronger and the blood flow becomes more powerful.
Thanks to an innovative approach combining light and electron microscopy, Julien Vermot’s team could measure the deflection of the cilia depending on the strength of the flow and simultaneously reconstruct their 3D internal architecture of a cilium. This allowed them to predict the mechanical properties of this structure and to highlight their extraordinary sensitivity. Indeed, cilia found on endothelial cells are three times more flexible than similar structures in the adult organism, such as those in the kidney, thus enabling them to detect very small variations in flow. At the cellular level, cilia bending results in an increase in the calcium concentration inside the cell, which is likely to activated signaling pathways necessary for correct vascular development.
For the first time in vivo, these results demonstrate the essential role of cilia on endothelial cells in early stages of development of the vascular system. They offer insight in to the understanding of blood vessel formation, a particularly important process in tumor progression. Indeed, just like the healthy tissue, a tumor requires oxygen and nutrients to continue to grow and inducing the formation of new vessels is one way to achieve this. With further exploration, these results may also shed new light on the molecular mechanisms leading to atherosclerosis, a disease responsible for the majority of cardiovascular diseases, in which endothelial cilia could be involved.