The roles of podoplanin and clec-2 in the development and maintenance of the cerebral vasculature

Lowe, Kate (2015). The roles of podoplanin and clec-2 in the development and maintenance of the cerebral vasculature. University of Birmingham. Ph.D.

This is the latest version of this item.

[img]
Preview
Lowe15PhD.pdf
PDF - Accepted Version

Download (10MB)

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.

Type of Work: Thesis (Doctorates > Ph.D.)
Award Type: Doctorates > Ph.D.
Supervisor(s):
Supervisor(s)EmailORCID
Watson, Steve P.UNSPECIFIEDUNSPECIFIED
Licence:
College/Faculty: Colleges (2008 onwards) > College of Medical & Dental Sciences
School or Department: School of Clinical and Experimental Medicine, Centre for Cardiovascular Sciences
Funders: Medical Research Council
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
URI: http://etheses.bham.ac.uk/id/eprint/5791

Available Versions of this Item

  • The roles of podoplanin and clec-2 in the development and maintenance of the cerebral vasculature. (deposited 27 Apr 2015 10:18) [Currently Displayed]

Actions

Request a Correction Request a Correction
View Item View Item

Downloads

Downloads per month over past year