The role of lipid phosphate phosphatases and their putative receptors in germ cell migration and survival in Drosophila melanogaster
During development, a variety of cell types undertake a guided migration to their target location and, consequently, display motile, proliferative and invasive behaviours. Failure in guided migration can result in severe developmental errors, including the formation of metastatic cancers or, in the case of germ cells, congenital defects. Primordial germ cells (PGCs) are the germ line stem cell progenitors that produce the gametes and pass the genetic material from generation to generation. In Drosophila melanogaster, as in many other organisms, the PGCs are set-aside at the beginning of embryogenesis as a distinct sub-set of cells that are easily detectable by immunochemical means. As such, they provide a good system in which to study the control of cell migration during development. Furthermore, since they are subject to various cell death and cell survival signals during their journey, they provide an opportunity to study the regulation of stem cell survival in vivo. wunen and wunen-2 encode lipid phosphate phosphatases (LPPs) and regulate Drosophila PGC survival and migration. LPP-like activity has been detected in all cell and tissue types so far studied, but remarkably little is known of their biological functions, and their physiological substrates remain elusive. The first aim of this work was to investigate differences in substrate recognition between Drosophila Wunen and the mammalian LPP isoforms, both in vitro, by means of biochemical assays and in vivo, by examining the ability of the mammalian isoforms to recognise the same physiological substrate as Wunen in Drosophila embryos. It also investigates hetero- and homo- oligomerisation of the fly and mammalian LPPs as a possible mechanism of action. In order to fully understand these proteins, it is necessary to identify and characterise their receptors. This work identifies a G protein-coupled receptor involved in Drosophila PGC migration and survival, and investigates its possible relationship to Wunen.