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Title: Cell dynamics and cell-matrix interactions during neural tube closure
Author: Mole, M. A.
ISNI:       0000 0004 7964 799X
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2017
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During development the neuroepithelium bends and fuses dorsally to form the neural tube, precursor of the brain and spinal cord. The current study focused on the role of cellextracellular matrix (ECM) interactions and cell dynamics during neural tube morphogenesis. ECM-integrin interactions have long been thought to play a role in neural tube closure, but there has been little experimental analysis. In this study, the initial aim was to identify the ECM constituents and integrin receptors expressed during neurulation and to define their tissue source of expression and protein localisation. This revealed a significant upregulation of the major integrins at the site of zippering. To address the potential role of ECM-integrin interactions at this site, a conditional approach was used to delete the central receptor subunit, integrin β1, from either the dorsal neural tube or surface ectoderm. Deletion of integrin β1 prevented neural tube closure leading to exencephaly and spina bifida. A model based on loss of dorsal anchorage between surface ectoderm and neural tube was proposed as potential causative mechanism underlying failure of neural tube closure. During neurulation, the formation of dorsolateral hinge points is characterized by a cell number increase in the dorsal neuroepithelium. The hypothesis that neuroepithelial cells may translocate dorsally was tested by vital fluorescent dye labelling. This demonstrated for the first time that cells migrate within the plane of the neuroepithelium from the mid-ventral to the most dorsal regions during the onset of dorsolateral bending. In vivo live imaging confirmed the above pattern of cell dynamics and further showed the presence of two main streams of cell migration, rostro-dorsally and caudally directed, identifying fundamentally different cell behaviours in the neuroepithelium, depending on rostro-caudal position.
Supervisor: Copp, A. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available