Fluid forces shape the embryonic heart: Insights from zebrafish

Abstract

Heart formation involves a complex series of tissue rearrangements, during which regions of the developing organ expand, bend, converge, and protrude in order to create the specific shapes of important cardiac components. Much of this morphogenesis takes place while cardiac function is underway, with blood flowing through the rapidly contracting chambers. Fluid forces are therefore likely to influence the regulation of cardiac morphogenesis, but it is not yet clear how these biomechanical cues direct specific cellular behaviors. In recent years, the optical accessibility and genetic amenability of zebrafish embryos have facilitated unique opportunities to integrate the analysis of flow parameters with the molecular and cellular dynamics underlying cardiogenesis. Consequently, we are making progress toward a comprehensive view of the biomechanical regulation of cardiac chamber emergence, atrioventricular canal differentiation, and ventricular trabeculation. In this review, we highlight a series of studies in zebrafish that have provided new insight into how cardiac function can shape cardiac morphology, with a particular focus on how hemodynamics can impact cardiac cell behavior. Over the long term, this knowledge will undoubtedly guide our consideration of the potential causes of congenital heart disease.

Defective heart chamber growth and myofibrillogenesis after knockout of adprhl1 gene function by targeted disruption of the ancestral catalytic active site

“…Directed hypertrophy determines the overall shape of a chamber while cell division is more evident during ballooning stages in mammalian hearts that undergo rapid increases in size [ 6 ]. Outgrowth occurs as the linear heart has already commenced peristaltic beating and zebrafish studies have shown that blood fluid forces can influence final chamber morphology by affecting cytoskeletal protein localization, cardiomyocyte maturation and also endocardial proliferation [ 7 , 8 , Reviewed 9 ]. Underpinning the directed growth is myofibrillogenesis, the process of assembling the contractile protein machinery within the muscle cells.…”

Cardiac function modulates endocardial cell dynamics to shape the cardiac outflow tract

“…Another intriguing possibility is that particular patterns of blood pressure could stretch endocardial cells in a manner that provokes specific cellular responses. In future work, a combination of techniques that directly manipulate flow direction or induce stretch (Anton et al, 2013;Marjoram et al, 2016;Sidhwani & Yelon, 2019), together with controlled flow environments to house explanted hearts (Cao & Poss, 2016;Wong et al, 2016), could enable the dissection of potential influences of specific functional cues on OFT morphogenesis.…”

“…The embryonic heart serves as an important example of how biomechanical cues enforce organ form (Collins & Stainier, 2016;Lindsey et al, 2014;Sidhwani & Yelon, 2019). As blood flows through the cardiac chambers, it sloshes along the grooves and gorges created by the inner endocardial layer of the heart.…”

The Shape and Function of Solid Fascias Depend on the Presence of Liquid Fascias

“…The morphogenesis of the cardiac structure is based on the thrust of the fluids. The shear stress deriving from the flow of fluids specularly determines the shape of the cell, while the pressure of the fluids themselves determine the boundaries and functions of the cell itself: the fluids shape the form and function at the embryological level [20]. Another study confirms this concept, where researchers demonstrate that fluids and their behavior stimulate correct cell division during embryogenesis [21].…”