VEGF signals induce trailblazer cell identity that drives neural crest migration

McLennan, Rebecca; Schumacher, Linus J.; Morrison, Jason A.; Teddy, Jessica M.; Ridenour, Dennis A.; Box, Andrew; Semerad, Craig L.; Li, Hua; McDowell, William; Kay, David; Maini, Philip K.; Baker, Ruth E.; Kulesa, Paul M.

doi:10.1016/j.ydbio.2015.08.011

Cited by 77 publications

(86 citation statements)

References 42 publications

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“…We observed a significant down-regulation of VEGFR1 and a trend for lower gene expression of other VEGF family members in the BAV ascending aorta. VEGF signaling is also known to play a role in migration of NCC36. Therefore, it is tempting to speculate that downregulation of VEGF signaling in BAV is associated with the improper termination of cushion EndMT and/or signals related to the migration of NCC.…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves

Maleki

Kjellqvist

Paloschi

et al. 2016

Sci Rep

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Individuals with a bicuspid aortic valve (BAV) are at significantly higher risk of developing aortic complications than individuals with tricuspid aortic valves (TAV) and defective signaling during the embryonic development and/or life time exposure to abnormal hemodynamic have been proposed as underlying factors. However, an explanation for the molecular mechanisms of aortopathy in BAV has not yet been provided. We combined proteomics, RNA analyses, immunohistochemistry, and electron microscopy to identify molecular differences in samples of non-dilated ascending aortas from BAV (N = 62) and TAV (N = 54) patients. Proteomic analysis was also performed for dilated aortas (N = 6 BAV and N = 5 TAV) to gain further insight into the aortopathy of BAV. Our results collectively showed the molecular signature of an endothelial/epithelial-mesenchymal (EndMT/EMT) transition-like process, associated with instability of intimal cell junctions and activation of RHOA pathway in the intima and media layers of ascending aorta in BAV patients. We propose that an improper regulation of EndMT/EMT during the spatiotemporally related embryogenesis of semilunar valves and ascending aorta in BAV individuals may result in aortic immaturity and instability prior to dilation. Exasperation of EndMT/EMT state in post embryonic life and/or exposure to non-physiological hemodynamic could lead to the aneurysm of ascending aorta in BAV individuals.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves

Maleki

Kjellqvist

Paloschi

et al. 2016

Sci Rep

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“…4–8 Typically, this involves using a computational model to simulate a population of agents on a two-dimensional surface, or in a three-dimensional volume. The agents in the ABM represent cells, and each agent is able to move and interact with other agents in the ABM.…”

Section: Introductionmentioning

confidence: 99%

Using approximate Bayesian computation to quantify cell–cell adhesion parameters in a cell migratory process

et al. 2017

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In this work, we implement approximate Bayesian computational methods to improve the design of a wound-healing assay used to quantify cell–cell interactions. This is important as cell–cell interactions, such as adhesion and repulsion, have been shown to play a role in cell migration. Initially, we demonstrate with a model of an unrealistic experiment that we are able to identify model parameters that describe agent motility and adhesion, given we choose appropriate summary statistics for our model data. Following this, we replace our model of an unrealistic experiment with a model representative of a practically realisable experiment. We demonstrate that, given the current (and commonly used) experimental set-up, our model parameters cannot be accurately identified using approximate Bayesian computation methods. We compare new experimental designs through simulation, and show more accurate identification of model parameters is possible by expanding the size of the domain upon which the experiment is performed, as opposed to increasing the number of experimental replicates. The results presented in this work, therefore, describe time and cost-saving alterations for a commonly performed experiment for identifying cell motility parameters. Moreover, this work will be of interest to those concerned with performing experiments that allow for the accurate identification of parameters governing cell migratory processes, especially cell migratory processes in which cell–cell adhesion or repulsion are known to play a significant role.

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“…However, measurements of chick cranial neural crest in vivo by McLennan et al also show that cells at the front of the invading neural crest express different genes than trailing cells [51]. This leader-follower expression difference is not reproduced in culture unless cells are exposed to the chemoattractant VEGF, and even then, the genes activated in leader and follower differ between in vitro and in vivo experiments, suggesting the importance of the local environment [52]. The results of McLennan et al emphasize potential differences between in vitro and in vivo mechanisms and reminds us of the importance of understanding multiple populations of cells, such as the distinctions between leaders and followers McLennan et al highlight and model [51, 52].…”

Section: Combining Chemotaxis and Collective Migration: Experimental mentioning

confidence: 99%

“…This leader-follower expression difference is not reproduced in culture unless cells are exposed to the chemoattractant VEGF, and even then, the genes activated in leader and follower differ between in vitro and in vivo experiments, suggesting the importance of the local environment [52]. The results of McLennan et al emphasize potential differences between in vitro and in vivo mechanisms and reminds us of the importance of understanding multiple populations of cells, such as the distinctions between leaders and followers McLennan et al highlight and model [51, 52]. Other researchers have also studied the leader-follower distinction in collective migration [26, 53, 54].…”

Section: Combining Chemotaxis and Collective Migration: Experimental mentioning

confidence: 99%

“…Fewer informed cells can be beneficial in the example McLennan et al study, as cells are sensing a gradient that extends over a relatively small range – only a few cell lengths – so cells far away from the front are ill-informed, and are better served by following their neighbors. A second study by this group models switching between leaders and followers [52]. …”

Section: Models To Consider: What Is Consistent With Experiment?mentioning

confidence: 99%

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Collective gradient sensing and chemotaxis: modeling and recent developments

Camley

2018

J. Phys.: Condens. Matter

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Cells measure a vast variety of signals, from their environment’s stiffness to chemical concentrations and gradients; physical principles strongly limit how accurately they can do this. However, when many cells work together, they can cooperate to exceed the accuracy of any single cell. In this Topical Review, I will discuss the experimental evidence showing that cells collectively sense gradients of many signal types, and the models and physical principles involved. I also propose new routes by which experiments and theory can expand our understanding of these problems.

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VEGF signals induce trailblazer cell identity that drives neural crest migration

Cited by 77 publications

References 42 publications

Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves

Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves

Using approximate Bayesian computation to quantify cell–cell adhesion parameters in a cell migratory process

Collective gradient sensing and chemotaxis: modeling and recent developments

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