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Title: PDGF signalling during Neural Crest Cell migration
Author: Bahm, Isabel
ISNI:       0000 0004 7229 3893
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2018
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Neural crest cells are a transient cell population, which migrates through the vertebrate embryonic body, and eventually gives rise to a many different cell types in the adult. Contact inhibition of locomotion (CIL) is a fundamental property of the collective migrating neural crest cells. CIL describes a process by which colliding cells change their direction upon collision and move away from each other, which has been linked to cell dispersion, boundary formation and metastasis. CIL is acquired in neural crest cells during Epithelial-to-Mesenchymal-Transition (EMT), by a switch in the expression of cadherins, from E to N-cadherin. To examine what governs this change I study PDGF signalling during Xenopus laevis cranial neural crest migration. Here I show that PDGFRα and its ligand PDGF-A are expressed in pre-migratory and migrating cranial neural crest cells. Inhibition of PDGF-A/PDGFRα impairs neural crest migration in vivo and cell dispersion in vitro. I find that PDGFRα inhibition leads to a decrease of N-cadherin levels in neural crest cells. Further, I demonstrate that PDGFRα signalling controls N-cadherin dependent CIL. This cellular response is controlled by the PI3K/AKT signalling pathway as a downstream effector of the PDGFRα cellular response in cranial neural crest cells. This data lead me to propose a novel mechanism by which PDGF signalling as a tissue-autonomous regulator of EMT is regulating N-cadherin dependent CIL during cranial neural crest cell migration in Xenopus laevis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available