Multiple Roles for CXCL12/CXCR4 Signalling in Cardiovascular Development

The cytokine CXCL12 signals via receptors CXCR4 and CXCR7 and is involved in many processes including stem cell homing, metastasis, collective cell migration, neurogenesis, remote ischaemic preconditioning, and cardiovascular development. Our published work in the area explored the role of the pathway downstream of TBX1, and also demonstrated that the pathway was essential for development of the coronary arteries beyond a capillary plexus.

The seminar will describe our unpublished work focusing upon semilunar valve development. The cell types and mechanisms underpinning valve development will be summarised, followed by an indication of how CXCL12-CXCR4 signalling affects these processes and the different lineages. In particular, defects of cell migration and cell polarity disturbances will be described. Evidence will be given to show how early dysmorphogenesis may, via altered flow, feedback to exacerbate the problem. Varied roles have been ascribed to CXCR7 e.g. co-signalling with CXCR4, signalling independently of CXCR4 (and CXCL12), and acting as a sink for CXCL12 ligand. Additional analysis of mouse mutants will be described that indicate why apparently antagonistic processes may result in a similar phenotype. The data will be discussed in light of work being conducted elsewhere on neural progenitor migration and coronary vessel formation.