Chemokines and their receptors (GPCRs –G-Protein Coupled Receptors) play important roles in biological processes such as embryonic development, inflammation, immunity and cancer. Therefore, a great amount of effort is directed to study their function and regulation. The SDF1 chemokine receptors, CXCR4 and CXCR7, are expressed by a wide range of human metastasis. They can also act as co-receptors for HIV-1 infection. Thus, these GPCRs have become important therapeutic targets. Tumour metastasis, as well as morphogenesis and wound healing involve the migration of cells as highly organized three-dimensional groups or as tissues. One such tissues is the zebrafish posterior lateral line primordium (pLLP), a group of about 100 cells that performs a stereotyped migration along the flanks of the embryo. As it migrates, the pLLP undergoes morphogenesis to generate seven to eight mechanosensory hair cell organs that it leaves in its wake. The pLLP migrates along a stripe of SDF1. CXCR4b is required at the leading edge while CXCR7 is expressed exclusively in the trailing cells which slow down and are deposited. Using the pLLP migration as a model system, I intend to study in vivo how the differential activation of two GPCRs responding to SDF1 can control different cell behaviours.
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