[Mechanotransduction of hemodynamic forces regulates organogenesis].
Endothelial cells (EC) of the vertebrate cardiovascular system (CVS) are bona fide, yet enigmatic mechanoreceptors. When cultured in vitro and exposed to fluid forces, EC modify their physiological behaviour at the structural, metabolical and gene expression levels in response to the mechanical stimulus. However, as a direct consequence of the hypoxic bias (and often the lethality) that results from blocking blood flow in most animal systems, the in vivo role of EC mechanosensation (ECMS) remains poorly understood. The zebrafish has recently emerged as an alternative genetic model for the study of vertebrate development. Its striking ability to survive until larval stages in the absence of blood circulation circumveys the usual caveats that are inherent to CVS research, and offers the exciting opportunity to dissect the function of ECMS in vivo. Two groups have already uncovered an essential role for ECMS in zebrafish organogenesis, particularly in heart morphogenesis. In embryos in which intracardiac blood flow is genetically or physically compromised, several features of the normally developing heart, including valve formation, are specifically disrupted. In addition, impressive imaging studies of zebrafish hemodynamics demonstrate that the shear stress exerted upon the cardiac endothelium is largely in the range of the stimulus that in vitro activates cytoskelettal remodeling and gene expression changes in EC. Hence the cardiac phenotypes observed in vivo may indeed directly result from a lack of ECMS-dependent EC activity. These data shed first light on the role of ECMS in vivo. Notably, they also suggest that a number of human congenital cardiomyopathies may arise through abnormal fetal hemodynamics and/or EC sensory activity. Finally, these discoveries reinforce the too often neglected role of epigenetic factors (in this case, fluid forces) in the regulation of animal development.
Sidi
Samuel
S
Inserm U.368, Ecole Normale Supérieure, 46, rue d'Ulm, 75230 Paris 05, France. sidi@biologie.ens.fr
Rosa
Frédéric M
FM
D000818:Animals; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D006321:Heart / Q000196:embryology; D006439:Hemodynamics; D007668:Kidney / Q000201:enzymology; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D038081:Organogenesis / Q000502:physiology*