Role of vascular endothelial-cadherin in vascular morphogenesis

Gory-Fauré, Sylvie; Prandini, Marie-Hélène; Pointu, Hervé; Roullot, Valérie; Pignot-Paintrand, Isabelle; Vernet, Muriel; Huber, Philippe

doi:10.1242/dev.126.10.2093

Cited by 262 publications

(26 citation statements)

References 48 publications

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“…ECs express vascular-endothelial-cadherin (VE-cadherin), a homophilic, trans-membrane celladhesion molecule, which appears to play a crucial role in vascular patterning [18,19]. Besides its role in cell-cell adhesion, VE-cadherin has a signaling function that determines how ECs respond to VEGF-A.…”

Section: Experimental Backgroundmentioning

confidence: 99%

Contact-Inhibited Chemotaxis in De Novo and Sprouting Blood-Vessel Growth

et al. 2008

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Blood vessels form either when dispersed endothelial cells (the cells lining the inner walls of fully formed blood vessels) organize into a vessel network (vasculogenesis), or by sprouting or splitting of existing blood vessels (angiogenesis). Although they are closely related biologically, no current model explains both phenomena with a single biophysical mechanism. Most computational models describe sprouting at the level of the blood vessel, ignoring how cell behavior drives branch splitting during sprouting. We present a cell-based, Glazier–Graner–Hogeweg model (also called Cellular Potts Model) simulation of the initial patterning before the vascular cords form lumens, based on plausible behaviors of endothelial cells. The endothelial cells secrete a chemoattractant, which attracts other endothelial cells. As in the classic Keller–Segel model, chemotaxis by itself causes cells to aggregate into isolated clusters. However, including experimentally observed VE-cadherin–mediated contact inhibition of chemotaxis in the simulation causes randomly distributed cells to organize into networks and cell aggregates to sprout, reproducing aspects of both de novo and sprouting blood-vessel growth. We discuss two branching instabilities responsible for our results. Cells at the surfaces of cell clusters attempting to migrate to the centers of the clusters produce a buckling instability. In a model variant that eliminates the surface–normal force, a dissipative mechanism drives sprouting, with the secreted chemical acting both as a chemoattractant and as an inhibitor of pseudopod extension. Both mechanisms would also apply if force transmission through the extracellular matrix rather than chemical signaling mediated cell–cell interactions. The branching instabilities responsible for our results, which result from contact inhibition of chemotaxis, are both generic developmental mechanisms and interesting examples of unusual patterning instabilities.

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Section: Experimental Backgroundmentioning

confidence: 99%

Contact-Inhibited Chemotaxis in De Novo and Sprouting Blood-Vessel Growth

et al. 2008

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“…If the chemoattractant sensitivity of the endothelial cells is restricted to the interfaces between the endothelial cells and the surrounding ECM by means of a contact inhibition mechanism, the spheroids sprout in microvascular-network-like configurations. Although our group [11,13,34] and others [9,10,14,[35][36][37] have suggested numerous plausible alternative mechanisms for de novo vasculogenesis and sprouting, in absence of a definitive explanatory model of angiogenesis we have selected the contact inhibition model for pragmatic reasons: It agrees reasonably well with experimental observation [12,38], it focuses on a chemotaxis mechanism amenable to genetic analysis, and it has a proven applicability in studies of tumor angiogenesis [39], age-related macular degeneration [40], and toxicology [41].…”

Section: Resultsmentioning

confidence: 99%

Computational Screening of Tip and Stalk Cell Behavior Proposes a Role for Apelin Signaling in Sprout Progression

et al. 2016

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Angiogenesis involves the formation of new blood vessels by sprouting or splitting of existing blood vessels. During sprouting, a highly motile type of endothelial cell, called the tip cell, migrates from the blood vessels followed by stalk cells, an endothelial cell type that forms the body of the sprout. To get more insight into how tip cells contribute to angiogenesis, we extended an existing computational model of vascular network formation based on the cellular Potts model with tip and stalk differentiation, without making a priori assumptions about the differences between tip cells and stalk cells. To predict potential differences, we looked for parameter values that make tip cells (a) move to the sprout tip, and (b) change the morphology of the angiogenic networks. The screening predicted that if tip cells respond less effectively to an endothelial chemoattractant than stalk cells, they move to the tips of the sprouts, which impacts the morphology of the networks. A comparison of this model prediction with genes expressed differentially in tip and stalk cells revealed that the endothelial chemoattractant Apelin and its receptor APJ may match the model prediction. To test the model prediction we inhibited Apelin signaling in our model and in an in vitro model of angiogenic sprouting, and found that in both cases inhibition of Apelin or of its receptor APJ reduces sprouting. Based on the prediction of the computational model, we propose that the differential expression of Apelin and APJ yields a “self-generated” gradient mechanisms that accelerates the extension of the sprout.

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“…PCs and DCs were represented in cluster 3 as shown by Fgfr3 , Prox1 , and Hes5 expression ( Bermingham-McDonogh et al 2006 ; Hartman et al 2009 ; Hayashi et al 2010 ). Endothelial cells and melanocytes were captured in clusters 4 and 5 as evidenced by the expression of Cldn5 , Cdh5 , and Sox17 ( Gory-Fauré et al 1999 ; Morita et al 1999 ; Zhou et al 2015 ) and of Gsta4 , Pmel , and Ptgds ( Takeda et al 2006 ; Uehara et al 2009 ; Hellström et al 2011 ), respectively. Atoh1 , Pou4f3 , and Gfi1 ( Xiang et al 1997 ; Wallis et al 2003 ; Woods et al 2004 ) were DEGs of sensory HCs characteristic for cluster 6, whereas lateral SCs in cluster 7 expressed Gata2 , Fst , and Hs3st1 ( Lilleväli et al 2004 ; Hartman et al 2015 ; Son et al 2015 ).…”

Section: Resultsmentioning

confidence: 99%

Mapping the regulatory landscape of auditory hair cells from single-cell multi-omics data

et al. 2021

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Auditory hair cells transduce sound to the brain, and in mammals, these cells reside together with supporting cells in the sensory epithelium of the cochlea, called the organ of Corti. To establish the organ's delicate function during development and differentiation, spatiotemporal gene expression is strictly controlled by chromatin accessibility and cell type–specific transcription factors, jointly representing the regulatory landscape. Bulk sequencing technology and cellular heterogeneity obscured investigations on the interplay between transcription factors and chromatin accessibility in inner ear development. To study the formation of the regulatory landscape in hair cells, we collected single-cell chromatin accessibility profiles accompanied by single-cell RNA data from genetically labeled murine hair cells and supporting cells after birth. Using an integrative approach, we predicted cell type–specific activating and repressing functions of developmental transcription factors. Furthermore, by integrating gene expression and chromatin accessibility data sets, we reconstructed gene regulatory networks. Then, using a comparative approach, 20 hair cell–specific activators and repressors, including putative downstream target genes, were identified. Clustering of target genes resolved groups of related transcription factors and was used to infer their developmental functions. Finally, the heterogeneity in the single-cell data allowed us to spatially reconstruct transcriptional as well as chromatin accessibility trajectories, indicating that gradual changes in the chromatin accessibility landscape are lagging behind the transcriptional identity of hair cells along the organ's longitudinal axis. Overall, this study provides a strategy to spatially reconstruct the formation of a lineage-specific regulatory landscape using a single-cell multi-omics approach.

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Role of vascular endothelial-cadherin in vascular morphogenesis

Cited by 262 publications

References 48 publications

Contact-Inhibited Chemotaxis in De Novo and Sprouting Blood-Vessel Growth

Contact-Inhibited Chemotaxis in De Novo and Sprouting Blood-Vessel Growth

Computational Screening of Tip and Stalk Cell Behavior Proposes a Role for Apelin Signaling in Sprout Progression

Mapping the regulatory landscape of auditory hair cells from single-cell multi-omics data

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