Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.646171
Title: The roles of podoplanin and clec-2 in the development and maintenance of the cerebral vasculature
Author: Lowe, Kate
ISNI:       0000 0004 5361 0005
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2015
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Abstract:
The C-type lectin-like receptor, CLEC-2, is constitutively expressed on platelets, with reported expression on a number of leukocyte subsets in adult mice. Constitutive or platelet-specific deletion of CLEC-2 in mice induces cerebral haemorrhaging by midgestation. In this thesis, I investigated the basis of this defect, hypothesising that it is mediated by the loss of CLEC-2 activation by its endogenous ligand, podoplanin, expressed on the developing neural tube. Podoplaninfl/fl mice were crossed to mice expressing PGK-Cre to induce deletion of podoplanin at the two-cell stage. Developing blood vessels were visualized by 3-dimensional microscopy and found to be aberrantly patterned in CLEC-2- and podoplanin-deficient mice, culminating in widespread cerebral haemorrhaging by mid-gestation. Haemorrhages were also observed following Nestin-Cre driven deletion of podoplanin on neural progenitors and following deletion of the platelet integrin, αIIbβ3. Together these studies support that neuro-epithelial-derived podoplanin interacts with platelet-CLEC-2 to guide the maturation and integrity of the cerebral vasculature and to prevent haemorrhage by stimulating platelet aggregation. Using tamoxifen-inducible deletion of CLEC-2 in adult mice, the expression profile of CLEC-2 was investigated and shown to be restricted to platelets and circulating B-lymphocytes and CD11bhigh Gr1high myeloid cells. Furthermore, loss of CLEC-2 in adult mice was shown to be dispensable for maintaining blood-brain barrier permeability.
Supervisor: Not available Sponsor: Medical Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.646171  DOI: Not available
Keywords: Q Science (General) ; R Medicine (General)
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