Abstract
Vascular remodeling of the mouse embryonic yolk sac is a highly dynamic process dependent on multiple genetic signaling pathways as well as biomechanical factors regulating proliferation, differentiation, migration, cell-cell, and cell-matrix interactions. During this early developmental window, the initial primitive vascular network of the yolk sac undergoes a dynamic remodeling process concurrent with the onset of blood flow, in which endothelial cells establish a branched, hierarchical structure of large vessels and smaller capillary beds. In this review, we will describe the molecular and biomechanical regulators which guide vascular remodeling in the mouse embryonic yolk sac, as well as live imaging methods for characterizing endothelial cell and hemodynamic function in cultured embryos.
Highlights
The first functional organ system to form in mammalian embryos is the cardiovascular system
The direct role of the onset of blood flow at this early stage of vascular development has been studied for several years and is still highly debated; some suggested that blood flow is necessary for the transport of oxygen to the growing embryonic tissue, while others suspected blood flow in the nascent vasculature is required for the transport of soluble nutrients and growth factors essential for proper endothelial cell function (Conway et al, 2003)
Conditional knockout approaches directly targeting endothelial cells, cardiomyocytes, and/or hematopoietic cells, as well as imaging techniques, such as those described in this review, for in vivo analysis of hemodynamics and endothelial cell migration are all necessary when understanding the mechanism behind the complex morphological and molecular events that occur during vasculogenesis, angiogenesis, and vascular remodeling
Summary
The first functional organ system to form in mammalian embryos is the cardiovascular system. The early establishment of the cardiovascular network during development is a complex, morphogenetic process, which requires the regulation of multiple cell types and the activation of several signal transduction pathways If this network is not established properly, it affects organ development and embryo viability (Coultas et al, 2005; Udan et al, 2013a). After the blood islands have formed, angioblasts located at the outer edges divide and differentiate into endothelial cells and migrate distally into the yolk sac, forming a simple capillary network that encompasses the yolk sac This network of interconnected rudimentary small vessels, homogeneous in shape and size, is the primitive capillary plexus (Figure 1B) (Drake and Fleming, 2000; Coultas et al, 2005; Udan et al, 2013a). Several genetic studies in mice identified vascular endothelial receptor 2 (VEGFR2/Flk1) as a regulator of de novo vasculogenesis, critical for the development of both blood cells and the primitive www.frontiersin.org
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