Endothelial mechanotransduction in cardiovascular development and regeneration: emerging approaches and animal models

Living cells are exposed to multiple mechanical stimuli from the extracellular matrix or from surrounding cells. Mechanoreceptors are molecules that display status changes in response to mechanical stimulation, transforming physical cues into biological responses to help the cells adapt to dynamic changes of the microenvironment. Mechanical stimuli are responsible for shaping the tridimensional development and patterning of the organs in early embryonic stages. The development of the heart is one of the first morphogenetic events that occur in embryos. As the circulation is established, the vascular system is exposed to constant shear stress, which is the force created by the movement of blood. Both spatial and temporal variations in shear stress differentially modulate critical steps in heart development, such as trabeculation and compaction of the ventricular wall and the formation of the heart valves. Zebrafish embryos are small, transparent, have a short developmental period and allow for real-time visualization of a variety of fluorescently labeled proteins to recapitulate developmental dynamics. In this review, we will highlight the application of zebrafish models as a genetically tractable model for investigating cardiovascular development and regeneration. We will introduce our approaches to manipulate mechanical forces during critical stages of zebrafish heart development and in a model of vascular regeneration, as well as advances in imaging technologies to capture these processes at high resolution. Finally, we will discuss the role of molecules of the Plexin family and Piezo cation channels as major mechanosensors recently implicated in cardiac morphogenesis.