The Hippo signalling pathway coordinates organ growth and limits developmental variability by controlling dilp8 expression
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The Hippo signalling pathway coordinates organ growth and limits developmental variability by controlling dilp8 expression. / Boone, Emilie; Colombani, Julien; Andersen, Ditte S; Léopold, Pierre.
In: Nature Communications, Vol. 7, 22.11.2016, p. 13505.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 7
SP - 13505
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
ER -
ID: 212683216