Mechanosensitive Pathways in Heart Development: Findings from Chick Embryo Studies

Abstract

The heart is the first organ that starts to function in a developing embryo. It continues to undergo dramatic morphological changes while pumping blood to the rest of the body. Genetic regulation of heart development is partly governed by hemodynamics. Chick embryo is a major animal model that has been used extensively in cardiogenesis research. To reveal mechanosensitive pathways, a variety of surgical interferences and chemical treatments can be applied to the chick embryo to manipulate the blood flow. Such manipulations alter expressions of mechanosensitive genes which may anticipate induction of morphological changes in the developing heart. This paper aims to present different approaches for generating clinically relevant disturbed hemodynamics conditions using this embryonic chick model and to summarize identified mechanosensitive genes using the model, providing insights into embryonic origins of congenital heart defects.

Fetal Blood Flow and Genetic Mutations in Conotruncal Congenital Heart Disease

“…Hemodynamics can alter heart development independent of genetic or toxic exposures. Blood flow affects the expression of mechanosensitive genes and regulation of proteins [22][23][24][25][26], leading to abnormal valve formation [27,28] and heart defects, including TOF [16]. Despite extensive ongoing studies, the molecular mechanisms behind mechanosensitivity and mechanotransduction are not yet fully understood, in part due to the complexity of the signaling networks involved.…”

“…VEGF receptor 2 (VEGFR2, also known as KDR) is broadly expressed in the vascular endothelium and blood islands and is critical for their development [21][22][23][24]. The global VEGFR2 knockout is embryonic lethal between embryonic days 8.5 and 9.5 due to failure to form the blood islands or blood vessels [42].…”

Experimental assessment of cardiovascular physiology in the chick embryo

“…Thus, the chick embryo's heart and vasculature are visible and accessible for experimentation by removing a small piece of eggshell (Figure 1). Due to these attributes and the accessibility of chicken eggs, it is not surprising that the chick embryo has become established as a premier developmental animal model for studying cardiovascular physiology 14 and an excellent platform to explore the influences of hemodynamic forces within the cardiovascular system 15‐17 …”

Blood Flow Disturbance and Morphological Alterations Following the Right Atrial Ligation in the Chick Embryo

“…At early stages, the easy optical access to avian tissues allows researchers to monitor the blood flow where a surgical alteration may develop similar disease phenotypes with the human fetus. Many studies highlighted the efficiency of chick embryos to investigate the influence of disturbed hemodynamics on heart development ( Yalcin et al, 2010 , 2011 ; Henning et al, 2011 ; Alser et al, 2021 ; Salman et al, 2021 ) since chicken share identical molecular and morphological cascades of heart development with human ( Groenendijk et al, 2007 ; Katritsis et al, 2007 ). Left atrial ligation (LAL) is a well-established surgical technique performed upon chick embryos.…”