Abstract
Collective cell migration is a fundamental process, occurring during embryogenesis and cancer metastasis. Neural crest cells exhibit such coordinated migration, where aberrant motion can lead to fatality or dysfunction of the embryo. Migration involves at least two complementary mechanisms: contact inhibition of locomotion (a repulsive interaction corresponding to a directional change of migration upon contact with a reciprocating cell), and co-attraction (a mutual chemoattraction mechanism). Here, we develop and employ a parameterized discrete element model of neural crest cells, to investigate how these mechanisms contribute to long-range directional migration during development. Motion is characterized using a coherence parameter and the time taken to reach, collectively, a target location. The simulated cell group is shown to switch from a diffusive to a persistent state as the response-rate to co-attraction is increased. Furthermore, the model predicts that when co-attraction is inhibited, neural crest cells can migrate into restrictive regions. Indeed, inhibition of co-attraction in vivo and in vitro leads to cell invasion into restrictive areas, confirming the prediction of the model. This suggests that the interplay between the complementary mechanisms may contribute to guidance of the neural crest. We conclude that directional migration is a system property and does not require action of external chemoattractants.
Highlights
The Neural Crest (NC) is a multi-potent cell population that arises at the dorsal midline during embryo development, migrates ventrally through the embryo and is guided by strict migratory pathways [1]
In the presence of combination of repulsive (CIL) and co-attraction, directional migration occurred as a travelling wave of density, which reproduces the directional migration observed in real cells [12,14]
To test the relationship between directional collective migration, co-attraction and CIL, four cases were considered: (1) 2CIL,2CoA corresponding to an elimination of all processes except rotational turning, (2) +CIL,2CoA representing a complete knockdown of co-attraction, (3) 2CIL,+CoA which tests the model under the assumption that CIL is inhibited and (4) +CIL,+CoA corresponding to the baseline case (Figure 3a–d, Video S1)
Summary
The Neural Crest (NC) is a multi-potent cell population that arises at the dorsal midline during embryo development, migrates ventrally through the embryo and is guided by strict migratory pathways [1]. CIL can be described as a change in motion of individual cells due to contact, and occurs to differing extents in migratory cell types, such as fibroblasts [15,16,17], keratinocytes [22], Drosophila macrophages [23], NC [12,18,19,20,21] and the PC-3 cancer cell line [16,22,23,24] This process has been characterized in Xenopus, chick and zebrafish NC and has been demonstrated as a key mechanism that confers cell polarity, by regulating the activity of small GTPases, and controlling directional migration of the whole NC population [12,25]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
