Item

Abstract

Lysophospholipids are derivatives of phospholipids that include lysophosphatidic acid and sphingosine 1-phosphate. We are interested in understanding how such lipids act extracellularly to regulate cell behaviour including proliferation, survival and migration. Genetic screens have uncovered a role for lysophospholipids in germ cell migration. The wunen genes encode lipid phosphate phosphatases: transmembrane enzymes which can dephosphorylate lysophospholipids. They are located at the cell surface with their catalytic domain facing outside of the cell and thus are able to dephosphorylate extracellular substrates. Wunens act as germ cell repellents: Germ cells avoid wunen expressing somatic tissues. Our model is that germ cells require a lysophospholipid attractant that is destroyed by wunen expressing somatic cells. Recently we have uncovered a role for wunens in heart development. Wunens are strongly expressed in heart cells and in wunen mutants the heart is malformed. The heart is formed by coalescence of rows of heart cells which are initially located bilaterally but use dorsal closure events to move dorsally towards the midline and each other. We have analysed the movement and morphology of heart cells in wild-type and mutant. In the mutant we find that heart cells are specified properly and move towards the midline. In the majority of embryos all of the heart cells meet normally at the midline but in some embryos meeting at the midline is incomplete and small gaps remain. In both cases however the heart cells subsequently loose adhesion between rows generating a malformed heart. Our goal is to discern which and how lysophospholipids influence heart cell behaviour and to understand the extent of the similarities in germ and heart cell biology.