title: The Unc-5 Receptor Is Directly Regulated by Tinman in the Developing Drosophila Dorsal Vessel.
abstract: During early heart morphogenesis cardiac cells migrate in two bilateral opposing rows, meet at the dorsal midline and fuse to form a hollow tube known as the primary heart field in vertebrates or dorsal vessel (DV) in Drosophila. Guidance receptors are thought to mediate this evolutionarily conserved process. A core of transcription factors from the NK2, GATA and T-box families are also believed to orchestrate this process in both vertebrates and invertebrates. Nevertheless, whether they accomplish their function, at least in part, through direct or indirect transcriptional regulation of guidance receptors is currently unknown. In our work, we demonstrate how Tinman (Tin), the Drosophila homolog of the Nkx-2.5 transcription factor, regulates the Unc-5 receptor during DV tube morphogenesis. We use genetics, expression analysis with single cell mRNA resolution and enhancer-reporter assays in vitro or in vivo to demonstrate that Tin is required for Unc-5 receptor expression specifically in cardioblasts. We show that Tin can bind to evolutionary conserved sites within an Unc-5 DV enhancer and that these sites are required for Tin-dependent transactivation both in vitro and in vivo.
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland; Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Jamshid
authors.initials: J
authors.lastname: Asadzadeh
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland.
authors.forename: Niamh
authors.initials: N
authors.lastname: Neligan
authors.affiliation: Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America.
authors.forename: Judith J
authors.initials: JJ
authors.lastname: Canabal-Alvear
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland; Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Amanda C
authors.initials: AC
authors.lastname: Daly
authors.affiliation: Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, New Jersey, United States of America.
authors.forename: Sunita Gupta
authors.initials: SG
authors.lastname: Kramer
authors.affiliation: Smurfit Institute of Genetics, Trinity College Dublin, Dublin, Ireland; Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
authors.forename: Juan-Pablo
authors.initials: JP
authors.lastname: Labrador
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004330:Drosophila / Q000196:embryology* / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D006321:Heart / Q000196:embryology*; D032386:Myoblasts, Cardiac / Q000378:metabolism; D059372:Nucleotide Motifs; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; C102933:tin protein, Drosophila