title: The Hippo signalling pathway coordinates organ growth and limits developmental variability by controlling dilp8 expression.
abstract: Coordination of organ growth during development is required to generate fit individuals with fixed proportions. We recently identified Drosophila Dilp8 as a key hormone in coupling organ growth with animal maturation. In addition, dilp8 mutant flies exhibit elevated fluctuating asymmetry (FA) demonstrating a function for Dilp8 in ensuring developmental stability. The signals regulating Dilp8 activity during normal development are not yet known. Here, we show that the transcriptional co-activators of the Hippo (Hpo) pathway, Yorkie (Yki, YAP/TAZ) and its DNA-binding partner Scalloped (Sd), directly regulate dilp8 expression through a Hpo-responsive element (HRE) in the dilp8 promoter. We further demonstrate that mutation of the HRE by genome-editing results in animals with increased FA, thereby mimicking full dilp8 loss of function. Therefore, our results indicate that growth coordination of organs is connected to their growth status through a feedback loop involving Hpo and Dilp8 signalling pathways.
authors.affiliation: University Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06100, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Boone
authors.affiliation: University Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06100, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Colombani
authors.affiliation: University Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06100, France.
authors.forename: Ditte S
authors.initials: DS
authors.lastname: Andersen
authors.affiliation: University Nice Sophia Antipolis, CNRS, Inserm, iBV, Nice 06100, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Léopold
mesh_terms: D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D017353:Gene Deletion; D000072669:Gene Editing; D005786:Gene Expression Regulation / Q000502:physiology*; D005838:Genotype; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000099317:Hippo Kinases
chemical_list: D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C572149:insulin-like peptide 8, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases