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.
    Artificial Life 14, New York; 07/2014
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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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    • "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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