Lindsey, S. E. | bioRxiv Science

bioRxiv2022

High-Resolution Ultrasound and Speckle Tracking: a non-invasive approach to assess in vivo gastrointestinal motility during development

Gastrointestinal motor activity has been extensively studied in adults, conversely only few studies have investigated fetal motor skills. When the gastrointestinal tract starts to contract during the embryonic period and how this function evolves during development are not known. Here, we adapted a non-invasive high-resolution echography technique combined with speckle tracking analysis to examine the gastrointestinal tract motor activity dynamics during chick embryo development. We provided the first recordings of fetal gastrointestinal motility in living embryos. We found that although gastrointestinal contractions appear very early during development, they become synchronized only at the end of the fetal period. To validate this approach, we used various pharmacological inhibitors and BAPX1 gene overexpression in vivo. We found that the enteric nervous system determinates the onset of the synchronized contractions in the stomach. Moreover, alteration of smooth muscle fiber organization led to an impairment of this functional activity. Altogether, our findings show that non-invasive high-resolution echography and speckle tracking analysis allow visualizing and quantifying gastrointestinal motility during development and highlight the progressive acquisition of functional and coordinated gastrointestinal motility before birth.

developmental biology↗

bioRxiv2020

Experimental-based Computational Modeling Distinguishes Early Cardiac Outflow Tract Compensation Mechanisms

Mechanical forces are essential for proper growth and remodeling of the primitive pharyngeal arch arteries (PAAs) into the great vessels of the heart. Despite general acknowledgement of a link between abnormal hemodynamics and cardiac malformations, the direct correlation between hemodynamics and pharyngeal arch artery morphogenesis remains poorly understood. The elusiveness behind understanding hemodynamic-malformation links is largely due to the difficulty of performing isolated hemodynamic perturbations and quantifying key hemodynamic indices in-vivo. To overcome this issue, minimally invasive occlusion experiments were combined with three-dimensional anatomical models of development and in-silico testing of experimental phenomenon. This combined experimental-computational approach led to a mechanistic understanding of physiological compensation mechanisms in abnormal cardiac morphogenesis. Using our experimental-based framework, we detail morphological and hemodynamic changes twenty-four hours post vessel occlusion. To gain mechanistic insights into the dynamic vessel adaptation process, we perform in-silico occlusions which allow for quantification of instantaneous changes in mechanical loading. We follow the propagation of small defects in a single embryo Hamburger Hamilton (HH) Stage 18 embryo to a more serious defect in an HH29 embryo. Results demonstrate that abnormal PAA hemodynamics can precipitate abnormal cardiac function given the correct timing and location of injury. Following vessel occlusion, morphology changes along the arches are no longer a simple flow-mediated response but rather work to maintain a range of wall shear stress values. Occlusion of the presumptive aortic arch overrides natural growth mechanisms and prevents it from becoming the dominant arch of the aorta. Author SummaryThe developing great vessels transport flow from the heart to the rest of the body. Proper spatial temporal morphogenesis of the primitive paired vessels into the definitive outflow tract of the heart is critical for normal cardiac function. Malpatterning of the great vessels is highly prevalent in congenital heart defects and occurs in conjunction with other intracardiac malformations, such as impaired ventricle and valve development. In this work, we combine experimental-based computational modeling with theoretical adaptation principles. Our combined experimental-computational framework allows for the delineation of immediate and longer-term vascular remodeling as well as the physical mechanisms behind such changes. We show that a small flow obstruction originating within the developing vessels can propagate into structurally serious malformations with impaired functionality.

developmental biology↗