title: Lateral positioning at the dorsal midline: Slit and Roundabout receptors guide Drosophila heart cell migration.
abstract: Heart morphogenesis requires the coordinated regulation of cell movements and cell-cell interactions between distinct populations of cardiac precursor cells. Little is known about the mechanisms that organize cardiac cells into this complex structure. In this study, we analyzed the role of Slit, an extracellular matrix protein and its transmembrane receptors Roundabout (Robo) and Roundabout2 (Robo2) during morphogenesis of the Drosophila heart tube, a process analogous to early heart formation in vertebrates. During heart assembly, two types of progenitor cells align into rows and coordinately migrate to the dorsal midline of the embryo, where they merge to assemble a linear heart tube. Here we show that cardiac-specific expression of Slit is required to maintain adhesion between cells within each row during dorsal migration. Moreover, differential Robo expression determines the relative distance each row is positioned from the dorsal midline. The innermost CBs express only Robo, whereas the flanking pericardial cells express both receptors. Removal of robo2 causes pericardial cells to shift toward the midline, whereas ectopic robo2 in CBs drives them laterally, resulting in an unfused heart tube. We propose a model in which Slit has a dual role during assembly of the linear heart tube, functioning to regulate both cell positioning and adhesive interactions between migrating cardiac precursor cells.
authors.affiliation: Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, 675 Hoes Lane West, Piscataway, NJ 08854, USA.
authors.forename: Edgardo
authors.initials: E
authors.lastname: Santiago-Martínez
authors.forename: Nadine H
authors.initials: NH
authors.lastname: Soplop
authors.forename: Sunita G
authors.initials: SG
authors.lastname: Kramer
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology* / Q000196:embryology* / Q000502:physiology; D006321:Heart / Q000033:anatomy & histology / Q000196:embryology; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology; D019076:Transgenes; D000097905:Roundabout Proteins
chemical_list: D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D000097905:Roundabout Proteins; C421243:Robo2 protein, Drosophila; C066819:sli protein, Drosophila