Summary: | 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). The thesis explores three different types of models to understand collective cell migration of the neural crest cells. Chapter 2 provides a review of the current literature. Chapter 3 presents the experimental data that are used to develop the models and Chapters 4, 5 and 6 explore three different modelling approaches. In Chapter 6, a parameterized discrete element model of neural crest cells is employed to investigate how the mechanisms of contact inhibition of locomotion and co-attraction 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. This suggests that the interplay between the complementary mechanisms may contribute to guidance of the neural crest. Directional migration is a system property and does not require action of external chemoattractants. The results of the thesis suggest that the cranial neural crest cells could acheive collective cell migration by self-organisation that is caused by aggregation.
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