Roles of leader and follower cells in collective cell migration

Abstract

Collective cell migration is a widely observed phenomenon during animal development, tissue repair, and cancer metastasis. Considering its broad involvement in biological processes, it is essential to understand the basics behind the collective movement. Based on the topology of migrating populations, tissue-scale kinetics, called the “leader–follower” model, has been proposed for persistent directional collective movement. Extensive in vivo and in vitro studies reveal the characteristics of leader cells, as well as the special mechanisms leader cells employ for maintaining their positions in collective migration. However, follower cells have attracted increasing attention recently due to their important contributions to collective movement. In this Perspective, the current understanding of the molecular mechanisms behind the “leader–follower” model is reviewed with a special focus on the force transmission and diverse roles of leaders and followers during collective cell movement.

The cellular slime mold Fonticula alba forms a dynamic, multicellular collective while feeding on bacteria

“…These findings suggest a leader-follower organization. 23

Figure 2 Invasive collectives use a leader-follower organization (A) Brightfield images of a single invasive collective at the front over time. The yellow circle indicates an individual cell escaping the collective and yellow arrows indicate single cell tips.

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Nuclear export inhibition jumbles epithelial-mesenchymal states and gives rise to migratory disorder in healthy epithelia

“…Here, epithelial and mesenchymal characteristics extended far from the phenotypic center point. Meanwhile, typical follower cells manifest moderately high adhesion and moderately high protrusive ability (Desai et al, 2013; Qin et al, 2021). Therefore, it is possible that the degree of cooperation during concurrent E-M may ultimately depend on the distance of either E-M component from the phenotypic center.…”

“…Beyond disrupting this force balance, NEI changed conventional leader-follower relationships. Typically, leader cells exhibit lower intercellular adhesion, and previous studies suggest this is required to conduct their role as the primary drivers of migration (Qin et al, 2021; Matsuzawa et al, 2018), where they polarize front-back and generate most of the traction to propel the collective (Reffay et al, 2014; Trepat and Sahai, 2018). Here, we show that NEI maintained the gradient of intercellular adhesion, such that adhesions between leaders remained weaker than those between followers.…”

“…However, the increase in cell-cell adhesion by itself is presumably sufficient to disrupt the function of leader cells. In general, higher cell-cell adhesion predisposes cells to repolarization cues from neighbors and reduces the contribution of polarization stemming from mechanosensitive adhesion-based promotion of locomotion (Desai et al, 2013; Qin et al, 2021). Without appropriate polarization signals, leaders would not be able to effectively coordinate movement of the group.…”

“…Meanwhile, cells behind – the followers – supplement leader tractions. Whereas followers maintain better adhesion to neighbors, they also extend cryptic protrusions to help forwardly propel the collective (Qin et al, 2021; Repat and Sahai, 2018). What arises from these distinct cell populations is an EMT gradient that fundamentally supports migration (Sarker et al, 2019).…”