Multiscale mechanisms of cell migration during development: theory and experiment

Abstract

models, cell movement is encouraged by cell-cell contact, which may be manifested as nudging from behind (Davis and Trinkaus, 1981) or the detachment of cells at the front of a migratory cell sheet (Carmona-Fontaine et al., 2008) to create space. These cell behaviors alone may not produce directional movement of a multicellular stream, but when local inhibitory signals restrict cell movements the result can be long-distance directed cell movement.By contrast, other models suggest that cells respond to chemotactic signals that drive the directional migration of individual cells (Dormann and Weijer, 2003;Richardson and Lehmann, 2010;Tarbashevich and Raz, 2010;Roussos et al., 2011;Cai et al., 2012) or cell clusters (Valentin et al., 2007;Aman and Piotrowski, 2010;Streichan et al., 2011). In these models, cells may respond directly to a chemotactic signal or receive guidance from neighboring cells.As long-distance cell migration is a major aspect of embryonic development (Dormann and Weijer, 2003;Richardson and Lehmann, 2010;Tarbashevich and Raz, 2010;Kulesa and Gammill, 2010), adult morphogenesis (Hatten and Roussel, 2011), tissue repair (Burns and Steinberg, 2011) and cancer metastasis (Roussos et al., 2011;Friedl and Gilmour, 2009), the examination of this phenomenon could have significant implications for better understanding birth defects and disease. Yet, even with multiscale data collected from different model systems and emerging computational models, the cellular and molecular mechanisms of long distance cell migration are still unclear. This is due in part to a disconnect between theory and experiment that limits the testing of various hypotheses parametrised by biological data. Thus, what is needed is a fully integrative experimental-modeling approach that can reject certain hypotheses in favor of others and elucidate multiscale mechanisms of cell migration.Here, we examine how a subpopulation of embryonic cells travel long distances and respond to tissue growth to accurately reach a target. We study this question using the neural crest (NC) as our model experimental system. NC cells exit the dorsal neural tube (NT) and travel long distances throughout the developing embryo along stereotypical pathways rich in microenvironmental signals, mesoderm and extracellular matrix (Noden and Trainor, 2005;Perris and Perissinotto, 2000). The NC cell population is crucial for proper development of the face, heart and peripheral nervous systems, and is the cellular origin of the highly aggressive cancers, melanoma and neuroblastoma (Trainor, 2005;Sauka-Spengler and Bronner-Fraser, 2008;Gammill and Roffers-Agarwal, 2010;Kasemeier-Kulesa et al., 2008;Jiang et al., 2011 SUMMARYLong-distance cell migration is an important feature of embryonic development, adult morphogenesis and cancer, yet the mechanisms that drive subpopulations of cells to distinct targets are poorly understood. Here, we use the embryonic neural crest (NC) in tandem with theoretical studies to evaluate model mechanisms of long-distance cell migration....

Tactile interactions lead to coherent motion and enhanced chemotaxis of migrating cells

“…Recent studies have found that co-attraction between cells may play a role in collective migration [26,27]. This is also consistent with the framework of flocking models [9,10].…”

“…In loosely associated stream-like migration cell protrusions transmit biochemical signals. For neural crest cells, whose migration shares many characteristics with metastatic cancer cells, such interactions provide directional guidance that leads to coordinated migration even in the absence of external chemoattractant [6,[25][26][27]. When two cells touch a chemical exchange occurs and in response to this signalling, the protrusions at the site of contact collapse.…”

Complex Matrix Remodeling and Durotaxis Can Emerge From Simple Rules for Cell-Matrix Interaction in Agent-Based Models

“…The migration of cells on or through extracellular matrix (ECM) as well as cell-mediated remodeling of ECM underlie many biological processes including development [1], growth and remodeling [2], fibrotic pathologies [3], and wound healing [4] and are also important components of many tissue engineering applications [5,6]. In addition to chemical means such as the synthesis, modification, and degradation of the matrix, cells remodel (i.e., reorganize existing material) ECM using mechanical (or traction) forces.…”

Neural crest and cancer: Divergent travelers on similar paths

“…Additionally, in silico modeling has proposed that a balance of coattraction and CIL is important for the directional migration of NCCs (Woods et al, 2014). Other modeling suggests that NCCs may have two general roles: leader cells located toward the front of the migratory stream and follower cells trailing behind the leaders (McLennan et al, 2012). Based on this computational model, leader cells would respond more to long-range signals within the microenvironment, while follower cells would respond to short-range signals coming from NCCs ahead of them (McLennan et al, 2012).…”