title: Cdc42 is required in a genetically distinct subset of cardiac cells during Drosophila dorsal vessel closure.
abstract: The embryonic heart tube is formed by the migration and subsequent midline convergence of two bilateral heart fields. In Drosophila the heart fields are organized into two rows of cardioblasts (CBs). While morphogenesis of the dorsal ectoderm, which lies directly above the Drosophila dorsal vessel (DV), has been extensively characterized, the migration and concomitant fundamental factors facilitating DV formation remain poorly understood. Here we provide evidence that DV closure occurs at multiple independent points along the A-P axis of the embryo in a "buttoning" pattern, divergent from the zippering mechanism observed in the overlying epidermis during dorsal closure. Moreover, we demonstrate that a genetically distinct subset of CBs is programmed to make initial contact with the opposing row. To elucidate the cellular mechanisms underlying this process, we examined the role of Rho GTPases during cardiac migration using inhibitory and overexpression approaches. We found that Cdc42 shows striking cell-type specificity during DV formation. Disruption of Cdc42 function specifically prevents CBs that express the homeobox gene tinman from completing their dorsal migration, resulting in a failure to make connections with their partnering CBs. Conversely, neighboring CBs that express the orphan nuclear receptor, seven-up, are not sensitive to Cdc42 inhibition. Furthermore, this phenotype was specific to Cdc42 and was not observed upon perturbation of Rac or Rho function. Together with the observation that DV closure occurs through the initial contralateral pairing of tinman-expressing CBs, our studies suggest that the distinct buttoning mechanism we propose for DV closure is elaborated through signaling pathways regulating Cdc42 activity in this cell type.
authors.affiliation: Department of Pathology and Laboratory Medicine, Rutgers-Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA.
authors.forename: David
authors.initials: D
authors.lastname: Swope
authors.affiliation: Department of Pathology and Laboratory Medicine, Rutgers-Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Kramer
authors.affiliation: Department of Pathology and Laboratory Medicine, Rutgers-Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA; Graduate Program in Cell and Developmental Biology, Rutgers Graduate School of Biomedical Sciences at Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA.
authors.forename: Tiffany R
authors.initials: TR
authors.lastname: King
authors.affiliation: Department of Pathology and Laboratory Medicine, Rutgers-Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA.
authors.forename: Yi-Shan
authors.initials: YS
authors.lastname: Cheng
authors.affiliation: Department of Pathology and Laboratory Medicine, Rutgers-Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA; Graduate Program in Cell and Developmental Biology, Rutgers Graduate School of Biomedical Sciences at Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA. Electronic address: kramersg@rwjms.rutgers.edu.
authors.forename: Sunita G
authors.initials: SG
authors.lastname: Kramer
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006321:Heart / Q000196:embryology*; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008954:Models, Biological; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
chemical_list: C090145:Cdc42 protein, Drosophila; D029721:Drosophila Proteins; D019204:GTP-Binding Proteins
keywords: Cdc42; Dorsal vessel; Drosophila; Rho GTPase