The effects of reduced hemodynamic loading on morphogenesis of the mouse embryonic heart

Development of the embryonic heart involves an intricate network of biochemical and genetic cues to ensure its proper growth and morphogenesis. However, studies from avian and teleost models reveal that biomechanical force, namely hemodynamic loading (blood pressure and shear stress), plays a signif...

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Bibliographic Details
Published in:Developmental biology 2018-10, Vol.442 (1), p.127-137
Main Authors: Hoog, Tanner G., Fredrickson, Samantha J., Hsu, Chih-Wei, Senger, Steven M., Dickinson, Mary E., Udan, Ryan S.
Format: Article
Language:English
Subjects:
Heart morphogenesis
Hemodynamic load
Looping
Mouse embryo
Myocardium
Trabeculation
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Summary:Development of the embryonic heart involves an intricate network of biochemical and genetic cues to ensure its proper growth and morphogenesis. However, studies from avian and teleost models reveal that biomechanical force, namely hemodynamic loading (blood pressure and shear stress), plays a significant role in regulating heart development. To study how hemodynamic loading impacts development of the mammalian embryonic heart, we utilized mouse embryo culture and manipulation techniques and performed optical projection tomography imaging followed by morphometric analysis to determine how reduced-loading affects heart volume, myocardial thickness, trabeculation and looping. Our results reveal that hemodynamic loading can regulate these features at different thresholds. Intermediate levels of hemodynamic loading are sufficient to promote proper myocardial growth and heart size, but insufficient to promote looping and trabeculation. Whereas, low levels of hemodynamic loading fails to promote proper growth of the myocardium and heart size. These results reveal that the regulation of heart development by biomechanical force is conserved across many vertebrate classes, and this study begins to elucidate how these specific forces regulate development of the mammalian heart. [Display omitted] •Normal hemodynamic loading is required for proper development of mouse heart.•Low levels of hemodynamic load reduces myocardial thickness and heart volume.•Treatment of embryos with acrylamide diminishes hematocrit and hemodynamic load.•Intermediate levels of hemodynamic load impairs cardiac looping and trabeculation.
ISSN:0012-1606
1095-564X
DOI:10.1016/j.ydbio.2018.07.007