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| Status |
Public on Aug 25, 2018 |
| Title |
Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth |
| Organism |
Danio rerio |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
The Hippo pathway and its nuclear effector Yap regulate organ size and cancer formation. While many modulators of Hippo activity have been identified, little is known about how Yap target genes mediate these growth effects. Here, we show that defects in hepatic progenitor potential and liver growth in yap-/- mutant zebrafish are caused by impaired glucose transport and nucleotide biosynthesis: transcriptomic and metabolomic analyses reveal that Yap directly regulates expression of glucose transporter glut1, causing decreased glycolytic flux into anabolic nucleotide biosynthesis in yap-/- mutants and impaired glucose tolerance in adults. Nucleotide supplementation improved Yap-deficient phenotypes, indicating functional importance of glucose-fuelled nucleotide biosynthesis. Yap-regulated Glut1 expression and glucose uptake are conserved in mammals. Our results identify Glut1 as a direct Yap target enhancing glucose uptake and utilization for anabolic nucleotide biosynthesis, which are required for organ growth. Our findings demonstrate the central role of Hippo signalling in metabolic homeostasis
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| Overall design |
WT, yap-/- and yap-/-;taz-/- mutant larvae at 3 dpf, 4 replicates each.
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| |
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| Contributor(s) |
Goessling W, Houvras Y |
| Citation missing |
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| Submission date |
Aug 24, 2018 |
| Last update date |
Jan 14, 2019 |
| Contact name |
Wolfram Goessling |
| Organization name |
Brigham and Women's Hospital
|
| Department |
Department of Medicine, Division of Genetics
|
| Street address |
77 Avenue Louis Pasteur
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL14875 |
Illumina HiSeq 2000 (Danio rerio) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA487785 |
| SRA |
SRP158775 |
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