The role of Endothelial Cell Specific Chemotaxis Regulator (ECSCR) in endothelial cell biology

Verissimo, Ana Raquel Andrade (2013). The role of Endothelial Cell Specific Chemotaxis Regulator (ECSCR) in endothelial cell biology. University of Birmingham. Ph.D.

Preview

Verissimo13PhD.pdf
PDF - Accepted Version
Download (5MB)

Abstract

Angiogenesis, although a natural process, when deregulated can be associated with many human pathologies, including cancer. The endothelial cells play a crucial role in the growth and remodelling of the vasculature. A novel unique endothelial marker, endothelial cell specific chemotaxis regulator (ECSCR), has been identified and the aim of this project was to characterise its expression patterns and mechanism of action.

In HUVECs the interaction with filamin A was confirmed and immunoprecipitation has pulled down several cytoskeletal proteins involved in cell movement, including moesin, that binds to ECSCR. ECSCR loss causes cytoskeleton to be disorganised and overexpression induces filopodia in HEK 293T cells, but not M2 cells, that do not contain filamin A.

In zebrafish ECSCR is restricted to the major trunk and head vasculature, whereas in mouse it appears to be present also in the intersegmental vessels. Morpholino mediated knockdown of zebrafish Escr caused disruption of intersegmental vessel sprouting from the trunk vessels. The original phenotype was successfully rescued. A null Ecscr knockout mouse has been produced and preliminary data show that the deletion is not lethal and ECSCR is present in some small vessels, but not all vasculature. Loss of ECSCR may result in respiratory complications.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):