The anaphylatoxin receptors in neural progenitor physiology

Abstract

The complement cascade is phylogenically ancient pathogen recognition and response system that forms the initial frontier of mammalian innate immunity. Complement forms the bridge between humoural and cellular immunity through the generation of the anaphylatoxins, C3a and C5a, to recruit leukocytes to a pathogenic insult. However, in recent years, novel roles for the complement system outside of innate immunity have been demonstrated, especially in the developing embryo.To add to these novel roles, this thesis explores the role of the complement anaphylatoxin receptors in neural development.Previous studies in our laboratory have indicated a novel role for C5aR1 in the prevention of neural tube defects in folate-deficient dams. In these studies, C5aR1 was localised to the neuroepithelium throughout the period of neural tube closure and the precursor to C5a, C5, was also shown to be present. It has previously been unclear, both in this study and others, what other components of the complement system are present in the developing embryo that may lead to the generation ofanaphylatoxins. Here we demonstrate that the classical and alternative pathways, at the time of murine neural tube closure, lack expression of key propagators. Our data demonstrate the C2/4-independent and extrinsic pathways remain patent as a plausible means of C5a generation.In order to trace C5aR1-expressing cells within the developing embryo, a transgenic mouse was