title: Genetic identification of intracellular trafficking regulators involved in Notch-dependent binary cell fate acquisition following asymmetric cell division.
abstract: Notch signalling is involved in numerous cellular processes during development and throughout adult life. Although ligands and receptors are largely expressed in the whole organism, activation of Notch receptors only takes place in a subset of cells and/or tissues and is accurately regulated in time and space. Previous studies have demonstrated that endocytosis and recycling of both ligands and/or receptors are essential for this regulation. However, the precise endocytic routes, compartments and regulators involved in the spatiotemporal regulation are largely unknown. In order to identify intracellular trafficking regulators of Notch signalling, we have undertaken a tissue-specific dsRNA genetic screen of candidates potentially involved in endocytosis and recycling within the endolysosomal pathway. dsRNA against 418 genes was induced in the Drosophila melanogaster sensory organ lineage in which Notch signalling regulates binary cell fate acquisition. Gain or loss of Notch signalling phenotypes were observed in adult sensory organs for 113 of them. Furthermore, 26 genes were found to regulate the steady state localisation of Notch, Sanpodo, a Notch co-factor, and/or Delta in the pupal lineage. In particular, we identified 20 genes with previously unknown function in D. melanogaster intracellular trafficking. Among them, we identified CG2747 and we show that it regulates the localisation of clathrin adaptor AP-1 complex, a negative regulator of Notch signalling. Together, our results further demonstrate the essential function of intracellular trafficking in regulating Notch-signalling-dependent binary cell fate acquisition and constitute an additional step toward the elucidation of the routes followed by Notch receptor and ligands during signalling.
authors: CNRS, UMR, Institut Génétique et Développement de Rennes, France. stephanie.lebras@univ-rennes1.fr
authors: Stéphanie
authors: S
authors: Le Bras
authors: Christine
authors: C
authors: Rondanino
authors: Géraldine
authors: G
authors: Kriegel-Taki
authors: Aurore
authors: A
authors: Dussert
authors: Roland
authors: R
authors: Le Borgne
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division / Q000235:genetics; D002454:Cell Differentiation; D019070:Cell Lineage; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D008024:Ligands; D010641:Phenotype; D012330:RNA, Double-Stranded / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D012679:Sense Organs / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D008024:Ligands; C497759:N protein, Drosophila; D012330:RNA, Double-Stranded; D051880:Receptors, Notch; D018808:Transcription Factor AP-1