Coordinating cell behaviour during blood vessel formation

Vascular Patterning Laboratory, Vesalius Research Center, VIB, 3000 Leuven, Belgium.
Development (Impact Factor: 6.46). 09/2011; 138(21):4569-83. DOI: 10.1242/dev.062323
Source: PubMed


The correct development of blood vessels is crucial for all aspects of tissue growth and physiology in vertebrates. The formation of an elaborate hierarchically branched network of endothelial tubes, through either angiogenesis or vasculogenesis, relies on a series of coordinated morphogenic events, but how individual endothelial cells adopt specific phenotypes and how they coordinate their behaviour during vascular patterning is unclear. Recent progress in our understanding of blood vessel formation has been driven by advanced imaging techniques and detailed analyses that have used a combination of powerful in vitro, in vivo and in silico model systems. Here, we summarise these models and discuss their advantages and disadvantages. We then review the different stages of blood vessel development, highlighting the cellular mechanisms and molecular players involved at each step and focusing on cell specification and coordination within the network.

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Available from: Ilse Geudens
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    • "When new vessel growth (angiogenesis) is needed, e.g., in development or wound healing, endothelial cells (ECs) lining blood vessel tubes adaptively respond to the release of diffusing growth factors from hypoxic (low in oxygen) tissue. The ECs then collectively coordinate such that some cells migrate and lead new tubular branches ( " sprouts " ), while others line the tube walls and ensure that the branches are well spaced (Geudens and Gerhardt 2011) (Fig. 1a). The selection of these two states - " active " or " inhibited " cell movement -is known to be coordinated by Notch-driven " lateral inhibition " , where cells battle to inhibit their neighbors (Hellström et al 2007, Jakobsson et al 2009). "
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    ABSTRACT: During morphogenesis (the generation of form), biological cells, agents or robots must collectively coordinate where and when to move. How to solve such complex, spatial problems in a timely manner, is fundamental to survival in biological organisms, though temporal regulators are largely unexplored. We take the generation of new blood vessel networks (angiogenesis) as our case study system, where tissues low in oxygen stimulate endothelial cells "ECs" (the inner lining of blood vessels) to grow new network branches. This requires ECs to take on heterogeneous states by collectively competing with one another for migratory status via lateral inhibition. We propose here that the traditional "decide then move" perspective of cell behavior in angiogenesis may miss a key temporal regulator as it is too slow to account for the rapid, adaptive assignment of heterogeneous cell states. Here we show that a "move and decide" view may provide a better account. In a study focused on an individual EC in a simulated collective, we find that active perception (sensorimotor feedback) can generate bistability through migration-induced cell shape changes. We further exemplify that when parameters affecting active perception are modulated, bistability is lost in the single cell. As a consequence, active perception can directly modulate collective decision timing.
    Full-text · Conference Paper · Jul 2014
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    • "Second, cells neighboring the tip cells are specified as stalk cells, which undergo proliferation, elongation and lumenization in order to shape the nascent vessel. The process of EC activation and tip/stalk cell selection is controlled to a large extent by crosstalk between vascular endothelial growth factors (VEGF) and Notch signaling, and the entire process of activation, migration and vessel elongation involves considerable cell-cell rearrangements, basement membrane decomposition and remodeling (for a detailed review, see Geudens and Gerhardt, 2011). The final stages of angiogenesis involve the recruitment of cells from the surrounding stroma, either perivascular cells that are destined for microvasculature or smooth muscle cells (SMCs) that are destined for larger vessels. "
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    ABSTRACT: The formation of vasculature is essential for tissue maintenance and regeneration. During development, the vasculature forms via the dual processes of vasculogenesis and angiogenesis, and is regulated at multiple levels: from transcriptional hierarchies and protein interactions to inputs from the extracellular environment. Understanding how vascular formation is coordinated in vivo can offer valuable insights into engineering approaches for therapeutic vascularization and angiogenesis, whether by creating new vasculature in vitro or by stimulating neovascularization in vivo. In this Review, we will discuss how the process of vascular development can be used to guide approaches to engineering vasculature. Specifically, we will focus on some of the recently reported approaches to stimulate therapeutic angiogenesis by recreating the embryonic vascular microenvironment using biomaterials for vascular engineering and regeneration.
    Preview · Article · Jul 2014 · Development
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    • "Correct filopodial guidance additionally relies on the semaphorin/VEGF coreceptor neuropilin 1 (Nrp1), which specifically recognizes heparin-binding isoforms of VEGF (Gu et al. 2003). Stalk cells are endothelial cells localized in the vascular sprout behind the tip cell and proliferate in a VEGF-dependent manner, thus ensuring elongation of the vascular sprout and formation of a vascular lumen (sumarized in Geudens and Gerhardt 2011). Specification of the vascular tip versus stalk cells is mediated by the Notch signaling pathway whereby interaction of the Delta-like 4 (Dll4) ligand with Notch-1/-4 receptors inhibits tip cell and promotes stalk cell differentiation (Phng and Gerhardt 2009). "
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    ABSTRACT: The blood-brain barrier (BBB) is essential for maintaining homeostasis within the central nervous system (CNS) and is a prerequisite for proper neuronal function. The BBB is localized to microvascular endothelial cells that strictly control the passage of metabolites into and out of the CNS. Complex and continuous tight junctions and lack of fenestrae combined with low pinocytotic activity make the BBB endothelium a tight barrier for water soluble moleucles. In combination with its expression of specific enzymes and transport molecules, the BBB endothelium is unique and distinguishable from all other endothelial cells in the body. During embryonic development, the CNS is vascularized by angiogenic sprouting from vascular networks originating outside of the CNS in a precise spatio-temporal manner. The particular barrier characteristics of BBB endothelial cells are induced during CNS angiogenesis by cross-talk with cellular and acellular elements within the developing CNS. In this review, we summarize the currently known cellular and molecular mechanisms mediating brain angiogenesis and introduce more recently discovered CNS-specific pathways (Wnt/β-catenin, Norrin/Frizzled4 and hedgehog) and molecules (GPR124) that are crucial in BBB differentiation and maturation. Finally, based on observations that BBB dysfunction is associated with many human diseases such as multiple sclerosis, stroke and brain tumors, we discuss recent insights into the molecular mechanisms involved in maintaining barrier characteristics in the mature BBB endothelium.
    Full-text · Article · Mar 2014 · Cell and Tissue Research
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