Cox AG, Tsomides A, Yimlamai D, Hwang KL, Miesfeld J, Galli GG, Fowl BH, Fort M, Ma KY, Sullivan MR, Hosios AM, Snay E, Yuan M, Brown KK, Lien EC, Chhangawala S, Steinhauser ML, Asara JM, Houvras Y, Link B, Vander Heiden MG, Camargo FD, Goessling W. 2018. Yap regulates glucose utilization and sustains nucleotide synthesis to enable organ growth. The EMBO journal. 37(22). Pubmed: 30348863 DOI:10.15252/embj.2018100294


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 the Yap target genes that mediate these growth effects. Here, we show that mutant zebrafish exhibit defects in hepatic progenitor potential and liver growth due to impaired glucose transport and nucleotide biosynthesis. Transcriptomic and metabolomic analyses reveal that Yap regulates expression of glucose transporter glut1, causing decreased glucose uptake and use for nucleotide biosynthesis in mutants, and impaired glucose tolerance in adults. Nucleotide supplementation improves Yap deficiency phenotypes, indicating functional importance of glucose-fueled nucleotide biosynthesis. Yap-regulated expression and glucose uptake are conserved in mammals, suggesting that stimulation of anabolic glucose metabolism is an evolutionarily conserved mechanism by which the Hippo pathway controls organ growth. Together, our results reveal a central role for Hippo signaling in glucose metabolic homeostasis.
© 2018 The Authors.

Related Faculty

Photo of Fernando Camargo

The Camargo laboratory focuses on the study of adult stem cell biology, organ size regulation, and cancer.

Photo of Wolfram Goessling

Wolfram Goessling uses the zebrafish model to study regulators of liver development and to explore endodermal progenitor cell specification, organ differentiation, and growth.

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