The Hippo signalling pathway coordinates organ growth and limits developmental variability by controlling dilp8 expression

TY - JOUR

T1 - The Hippo signalling pathway coordinates organ growth and limits developmental variability by controlling dilp8 expression

AU - Boone, Emilie

AU - Colombani, Julien

AU - Andersen, Ditte S

AU - Léopold, Pierre

PY - 2016/11/22

Y1 - 2016/11/22

N2 - 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.

AB - 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.

KW - Animals

KW - Cell Line

KW - Drosophila Proteins/genetics

KW - Drosophila melanogaster/genetics

KW - Gene Deletion

KW - Gene Editing

KW - Gene Expression Regulation/physiology

KW - Genotype

KW - Intercellular Signaling Peptides and Proteins/genetics

KW - Intracellular Signaling Peptides and Proteins/genetics

KW - Larva/genetics

KW - Protein-Serine-Threonine Kinases/genetics

KW - Signal Transduction

U2 - 10.1038/ncomms13505

DO - 10.1038/ncomms13505

M3 - Journal article

C2 - 27874005

SN - 2041-1723

VL - 7

SP - 13505

JO - Nature Communications

JF - Nature Communications

ER -