Follow-the-leader cell migration requires biased cell–cell contact and local microenvironmental signals

Abstract

Directed cell migration often involves at least two types of cell motility that include multicellular streaming and chain migration. However, what is unclear is how cell contact dynamics and the distinct microenvironments through which cells travel influence the selection of one migratory mode or the other. The embryonic and highly invasive neural crest (NC) are an excellent model system to study this question since NC cells have been observed in vivo to display both of these types of cell motility. Here, we present data from tissue transplantation experiments in chick and in silico modeling that test our hypothesis that cell contact dynamics with each other and the microenvironment promote and sustain either multicellular stream or chain migration. We show that when premigratory cranial NC cells (at the pre-otic level) are transplanted into a more caudal region in the head (at the post-otic level), cells alter their characteristic stream behavior and migrate in chains. Similarly, post-otic NC cells migrate in streams after transplantation into the pre-otic hindbrain, suggesting that local microenvironmental signals dictate the mode of NC cell migration. Simulations of an agent based model (ABM) that integrates the NC cell behavioral data predict that chain migration critically depends on the interplay of biased cell-cell contact and local microenvironment signals. Together, this integrated modeling and experimental approach suggests new experiments and offers a powerful tool to examine mechanisms that underlie complex cell migration patterns.

Cell traction in collective cell migration and morphogenesis: The chase and run mechanism

“…The size of the migratory collective depends on its position along the body axis: while in the head the cranial NC (CNC) forms larger collectively moving groups, in the trunk the streams can be as thin as a single cell and perform chain migration. 13 The migration of the trunk NC has been suggested to be driven by a leader cell, similar to what has been shown in angiogenic sprouting. 14 Here we focus on the CNC where this distinction of leader-follower cells is less clear and therefore which can be considered more of an emergent migratory property of this mesenchymal cell group.…”

Neural crest and cancer: Divergent travelers on similar paths

“…As cranial NCCs migrate along the rhombomeres, subpopulations migrate into and populate some of the branchial arches (Kuo and Erickson, 2010). The NCCs of the hyoid stream traverse over rhombomere 4 in a wide, densely packed stream, while those of the branchial stream migrate over rhombomere 7 in narrow, linear chain-like arrays (Wynn et al, 2013). Although these cells have different migratory characteristics, NCCs swapped between rhombomeres 4 and 7 in chick are able to adopt the local migratory style (Wynn et al, 2013).…”

“…The NCCs of the hyoid stream traverse over rhombomere 4 in a wide, densely packed stream, while those of the branchial stream migrate over rhombomere 7 in narrow, linear chain-like arrays (Wynn et al, 2013). Although these cells have different migratory characteristics, NCCs swapped between rhombomeres 4 and 7 in chick are able to adopt the local migratory style (Wynn et al, 2013). It is intriguing to consider what mechanisms are at play to enable the transplanted NCCs to adapt to their new microenvironments and take on local migratory patterns.…”

“…Several models have been put forward to explain the underlying mechanisms for NC migratory guidance, including leader-follower models (Wynn et al, 2013, 2012), chase-and-run (Theveneau et al, 2013), and contact inhibition of locomotion (CIL) (Carmona-Fontaine et al, 2008). While it is established that NCCs use guidance cues and the local extracellular matrix (ECM) to collectively migrate (Banerjee et al, 2013; McLennan et al, 2010), we lack a thorough mechanistic understanding of NCC collective migration and how it varies between subpopulations of NCCs destined for different locations and fates.…”

From classical to current: Analyzing peripheral nervous system and spinal cord lineage and fate

“…Second, electroporation and transgenesis techniques have emerged for labeling populations of neural crest cells with fluorescent tags like GFP or Red Fluorescent Protein (RFP) (Nie et al, 2011; Theveneau et al, 2010); RFP and fluorescent dextrans (Gross and Hanken, 2004) that have made possible high resolution confocal imaging (Kulesa et al, 2013; McKinney et al, 2013). These techniques have made it possible to study cell biological aspects of neural crest migration in many species, enabling the identification of ‘leaders’ and ‘followers’ and neural crest cell-cell interactions (Wynn et al, 2013) and examination of the developmental potential of neural crest cells at different times of exit from the neural tube (McKinney et al, 2013). Because these techniques unilaterally label the neural tube, they have revealed that contralaterally migrating neural crest cells are a major source of progenitor cells for the pain- and temperature-sensing afferents of the dorsal root ganglia (George et al, 2007).…”