Emergence of embryonic pattern through contact inhibition of locomotion

Abstract

SUMMARYThe pioneering cell biologist Michael Abercrombie first described the process of contact inhibition of locomotion more than 50 years ago when migrating fibroblasts were observed to rapidly change direction and migrate away upon collision. Since then, we have gleaned little understanding of how contact inhibition is regulated and only lately observed its occurrence in vivo. We recently revealed that Drosophila macrophages (haemocytes) require contact inhibition for their uniform embryonic dispersal. Here, to investigate the role that contact inhibition plays in the patterning of haemocyte movements, we have mathematically analysed and simulated their contact repulsion dynamics. Our data reveal that the final pattern of haemocyte distribution, and the details and timing of its formation, can be explained by contact inhibition dynamics within the geometry of the Drosophila embryo. This has implications for morphogenesis in general as it suggests that patterns can emerge, irrespective of external cues, when cells interact through simple rules of contact repulsion.

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

“…First, the noncohesive phase, in which cells are not in contact, might correspond to mesenchymal tissues. Experiments show that CIL leads to regular distributions of mesenchymal cells during development (24,25). This observation is consistent with the transition toward an ordered structure of cell clusters by increasing CIL strength ψ (Fig.…”

“…This interaction has been shown to be crucial in determining the collective behavior of cell groups in several contexts (22). For example, CIL guides the directional migration of neural crest cells (23) and also ensures the correct dispersion of Cajal-Retzius cells in the cerebral cortex (24) or of hemocytes in the embryo (25).Here, we model cellular interactions by means of an attraction due to intercellular adhesion and a soft repulsion associated to the reduction of cell-substrate adhesion area. In addition, CIL is modeled as an interaction orienting cell motility away from cell-cell contacts.…”

“…This interaction has been shown to be crucial in determining the collective behavior of cell groups in several contexts (22). For example, CIL guides the directional migration of neural crest cells (23) and also ensures the correct dispersion of Cajal-Retzius cells in the cerebral cortex (24) or of hemocytes in the embryo (25).…”

Cell migration: from tissue culture to embryos

“…CIL works to re-set the polarity of migrating cells. Cells initially sense contact with other cells either at the lamellipodium (Abercrombie, 1970;Abercrombie and Heaysman, 1954) or at longer distances through filopodial extensions (Carmona-Fontaine et al, 2008;Davis et al, 2012;Heckman, 2009;Lesseps et al, 1975;Steketee and Tosney, 1999;Teddy and Kulesa, 2004). Sensing is mediated by cell surface molecules, often cell-cell adhesion proteins of the cadherin family (Mayor and Carmona-Fontaine, 2010), which are proposed to change the balance in small GTPases, with local activation of RhoA at the cell-cell contact and suppression of Rac1 and repolarisation of the colliding cell (Nelson et al, 2004;Theveneau et al, 2010).…”

Coordinating cell polarity: heading in the right direction?

“…Although its role here is not yet known, Ds in other contexts was discussed at length, as described below. John Robert Davis (Stramer laboratory, King's College London, UK) described an 'intercellular clutch' that coordinates contact inhibition of locomotion between hemocytes in the Drosophila embryo (Davis et al, 2012). As two hemocytes migrate toward and contact each other, an adhesive junction is formed between them.…”