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Title: Complementing co-attraction : the role of the complement factor C9 in the collective migration of the neural crest
Author: McLachlan, S. A.
ISNI:       0000 0004 7660 218X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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Collective migration is a mode of cell movement that is important for a variety of biological processes such as wound healing, tissue morphogenesis and tumour invasion. The neural crest (NC) is a multipotent embryonic cell population that can serve as a model of collective cell migration. NC cells migrate as a cohesive group through the embryo before differentiating into a vast number of derivatives, from the neurons and glia of the peripheral nervous system, to the cartilage and bone of craniofacial structures. The complement cascade is primarily known for its role in innate immunity, acting as the first line of defence to pathogen invasion. However, recent evidence has also suggested a novel role for some complement cascade components (C3a and C3aR) as regulators of collective NC migration. Using Xenopus Laevis embryos, I have examined the importance of the terminal complement pathway protein, C9, for NC migration. I show that C9 is expressed within migrating NC and its inhibition is able to block NC migration in vivo. Also, C9 inhibition increases NC dispersion in in vitro culture and consequently disrupts the collective chemotactic responses of the NC. I show that this loss of collective behaviour on C9 inhibition is due to a reduction in the mutual cell attraction between NC cells, known as co-attraction. My results also suggest that the molecular mechanism for C9 function is similar to that found within the immune system, with both the secretion of C9 and the formation of the membrane attack complex (MAC) being important for its role within the NC. Overall, this thesis proposes a novel function for C9 in early development prior to the formation of the innate immune system.
Supervisor: Mayor, R. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available