Modelling collective cell migration of neural crest

Szabó, András; Mayor, Roberto

doi:10.1016/j.ceb.2016.03.023

Cited by 37 publications

(29 citation statements)

References 59 publications

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“…This model is consistent with experiments in avians in which vagal neural tube grafted into the sacral-level neural tube results in ENCCs migrating in the oral direction, into gut devoid of ENCCs [56]. Another potential mechanism linking cell density with wavefront migration is “contact inhibition of locomotion,” a process whereby cells that come into contact with each other stop migrating, repolarize, and migrate away from each other [71]. This has been observed when two neural crest cells meet, leading them to collapse their protrusions and alter their migratory direction [72], but has not been demonstrated in vagal ENCCs.…”

Section: Molecular and Cellular Control Of Ens Developmentsupporting

confidence: 84%

Enteric nervous system development: A crest cell’s journey from neural tube to colon

Nagy

Goldstein

2017

Seminars in Cell & Developmental Biology

185

134

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The enteric nervous system (ENS) is comprised of a network of neurons and glial cells that are responsible for coordinating many aspects of gastrointestinal (GI) function. These cells arise from the neural crest, migrate to the gut, and then continue their journey to colonize the entire length of the GI tract. Our understanding of the molecular and cellular events that regulate these processes has advanced significantly over the past several decades, in large part facilitated by the use of rodents, avians, and zebrafish as model systems to dissect the signals and pathways involved. These studies have highlighted the highly dynamic nature of ENS development and the importance of carefully balancing migration, proliferation, and differentiation of enteric neural crest-derived cells (ENCCs). Proliferation, in particular, is critically important as it drives cell density and speed of migration, both of which are important for ensuring complete colonization of the gut. However, proliferation must be tempered by differentiation among cells that have reached their final destination and are ready to send axonal extensions, connect to effector cells, and begin to produce neurotransmitters or other signals. Abnormalities in the normal processes guiding ENCC development can lead to failure of ENS formation, as occurs in Hirschsprung disease, in which the distal intestine remains aganglionic. This review summarizes our current understanding of the factors involved in early development of the ENS and discusses areas in need of further investigation.

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Section: Molecular and Cellular Control Of Ens Developmentsupporting

confidence: 84%

Enteric nervous system development: A crest cell’s journey from neural tube to colon

Nagy

Goldstein

2017

Seminars in Cell & Developmental Biology

185

134

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“…Nevertheless, some mesenchymal cells can also migrate collectively as a consequence of CIL (6,13,23) or of increased cell-cell adhesion (46). Therefore, these specific phenotypes might also correspond to the active polar liquid state.…”

Section: Discussion and Perspectivesmentioning

confidence: 99%

“…Here, we address this problem by means of large-scale simulations of self-propelled particles (SPP) endowed with interactions capturing generic cellular behaviors. Models of SPP with aligning interactions have been used to investigate collective cell motions in tissue monolayers (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). We extend this approach to unveil how the different structures and collective dynamics of cell colonies emerge from cell-cell interactions.…”

mentioning

confidence: 99%

Emergent structures and dynamics of cell colonies by contact inhibition of locomotion

Smeets

Alert

Pešek

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

106

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Cells in tissues can organize into a broad spectrum of structures according to their function. Drastic changes of organization, such as epithelial-mesenchymal transitions or the formation of spheroidal aggregates, are often associated either to tissue morphogenesis or to cancer progression. Here, we study the organization of cell colonies by means of simulations of self-propelled particles with generic cell-like interactions. The interplay between cell softness, cell-cell adhesion, and contact inhibition of locomotion (CIL) yields structures and collective dynamics observed in several existing tissue phenotypes. These include regular distributions of cells, dynamic cell clusters, gel-like networks, collectively migrating monolayers, and 3D aggregates. We give analytical predictions for transitions between noncohesive, cohesive, and 3D cell arrangements. We explicitly show how CIL yields an effective repulsion that promotes cell dispersal, thereby hindering the formation of cohesive tissues. Yet, in continuous monolayers, CIL leads to collective cell motion, ensures tensile intercellular stresses, and opposes cell extrusion. Thus, our work highlights the prominent role of CIL in determining the emergent structures and dynamics of cell colonies.self-propelled particles | cell-cell adhesion | contact inhibition of locomotion | cell monolayers | collective motion C ell colonies exhibit a broad range of phenotypes. In terms of structure, collections of cells can arrange into distributions of single cells, assemble into continuous monolayers or multilayered tissues, or even form 3D agglomerates. In terms of dynamics, cell motility may simply be absent or produce random, directed, or collective migration of cells. Transitions between these states of tissue organization are characteristic of morphogenetic events and are also central to tumor formation and dispersal (1-4). Therefore, a physical understanding of the collective behavior of cell colonies will shed light on the regulation of many multicellular processes involved in development and disease.However, a complete physical picture of multicellular organization is not yet available, partly due to the challenge of modeling the complex interactions between cells. Here, we address this problem by means of large-scale simulations of self-propelled particles (SPP) endowed with interactions capturing generic cellular behaviors. Models of SPP with aligning interactions have been used to investigate collective cell motions in tissue monolayers (5-18). We extend this approach to unveil how the different structures and collective dynamics of cell colonies emerge from cell-cell interactions.In addition to an excluded-volume repulsion, cells generally feature a short-range attraction as a consequence of their active cortical contractility transmitted through cell-cell junctions. With no additional interactions, this attraction would typically lead to cohesive tissues. However, not all cell types form cohesive tissues. Whereas epithelial cells tend to form continuous monolayers...

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“…Reverse engineering of how these individual cell movements lead to collective migration patterns has proved difficult. Whereas computational models are able to test whether a given set of ad hoc assumptions lead to emergence of observed patterns, these models usually ignore heterogeneity of cell responses, overlook complex behavior dynamics, and rarely perform quantitative comparisons with in vivo results (9)(10)(11)(12).…”

mentioning

confidence: 99%

Data-driven modeling reveals cell behaviors controlling self-organization during Myxococcus xanthus development

Cotter

Schüttler

Igoshin

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

145

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Collective cell movement is critical to the emergent properties of many multicellular systems, including microbial self-organization in biofilms, embryogenesis, wound healing, and cancer metastasis. However, even the best-studied systems lack a complete picture of how diverse physical and chemical cues act upon individual cells to ensure coordinated multicellular behavior. Known for its social developmental cycle, the bacterium Myxococcus xanthus uses coordinated movement to generate three-dimensional aggregates called fruiting bodies. Despite extensive progress in identifying genes controlling fruiting body development, cell behaviors and cell-cell communication mechanisms that mediate aggregation are largely unknown. We developed an approach to examine emergent behaviors that couples fluorescent cell tracking with datadriven models. A unique feature of this approach is the ability to identify cell behaviors affecting the observed aggregation dynamics without full knowledge of the underlying biological mechanisms. The fluorescent cell tracking revealed large deviations in the behavior of individual cells. Our modeling method indicated that decreased cell motility inside the aggregates, a biased walk toward aggregate centroids, and alignment among neighboring cells in a radial direction to the nearest aggregate are behaviors that enhance aggregation dynamics. Our modeling method also revealed that aggregation is generally robust to perturbations in these behaviors and identified possible compensatory mechanisms. The resulting approach of directly combining behavior quantification with data-driven simulations can be applied to more complex systems of collective cell movement without prior knowledge of the cellular machinery and behavioral cues.agent-based simulation | image processing | emergent behavior | fluorescent imaging | cell communication C ollective cell migration is essential for many developmental processes, including fruiting body development of myxobacteria (1) and Dictyostelium (2), embryonic gastrulation (3, 4), and neural crest development (5). Conversely, cancer cell metastases represent detrimental migratory events that disseminate dysfunctional cells (6). In all these processes, a population of cells leaves its current location and migrates in a coordinated manner to new locations where motility becomes reduced. Remarkable progress has been made in studying the intracellular machinery of these organisms (7). Much less is known about the systemlevel coordination of cell migration. Cell movement in these systems is a 3D, dynamic process coordinated by a combination of diverse physical and chemical cues acting on the cells (3,5,8). Recent developments in tracking individual cell movement in vivo have provided unprecedented detail and revealed surprising levels of heterogeneity (5, 7). Reverse engineering of how these individual cell movements lead to collective migration patterns has proved difficult. Whereas computational models are able to test whether a given set of ad hoc assumptions lead to e...

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Modelling collective cell migration of neural crest

Cited by 37 publications

References 59 publications

Enteric nervous system development: A crest cell’s journey from neural tube to colon

Enteric nervous system development: A crest cell’s journey from neural tube to colon

Emergent structures and dynamics of cell colonies by contact inhibition of locomotion

Data-driven modeling reveals cell behaviors controlling self-organization during Myxococcus xanthus development

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