The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal

By Bin Zhao, K. Tumaneng, K. Guan. Nature Cell Biology, 2011

1,180 citations recorded by the source corpus.

Precise control of organ size is crucial during animal development and regeneration. In Drosophila and mammals, studies over the past decade have uncovered a critical role for the Hippo tumour-suppressor pathway in the regulation of organ size. Dysregulation of this pathway leads to massive overgrowth of tissue. The Hippo signalling pathway is highly conserved and limits organ size by phosphorylating and inhibiting the transcription co-activators YAP and TAZ in mammals and Yki in Drosophila, key regulators of proliferation and apoptosis. The Hippo pathway also has a critical role in the self-renewal and expansion of stem cells and tissue-specific progenitor cells, and has important functions in tissue regeneration. Emerging evidence shows that the Hippo pathway is regulated by cell polarity, cell adhesion and cell junction proteins. In this review we summarize current understanding of the composition and regulation of the Hippo pathway, and discuss how cell polarity and cell adhesion proteins inform the role of this pathway in organ size control and regeneration.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/f6797de820c6b35d7815da6bfcbbe1d9b40515a2

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cell Biology

1. K. Guan
2. Fa-Xing Yu
3. Z. Meng
4. Randy L. Johnson
5. H. Park
6. Jung-Soon Mo
7. Toshiro Moroishi
8. Young Chul Kim

In Molecular Biology

1. E. Olson
2. K. Guan
3. Young Chul Kim
4. J. Richardson
5. R. Bassel-Duby
6. X. Qi
7. Fa-Xing Yu
8. Randy L. Johnson

Citations in the corpus

• Yap1 activation enables bypass of oncogenic Kras addiction in pancreatic cancer (2014, positive): “Yap1, a transcriptional coactivator and the downstreammediator of Hippo signaling, is regulated posttranscriptionally by either kinase-mediated degradation or cytoplasmic sequestration (Harvey et al., 2013; Zhao et al., 2011).”
• Hippo signaling disruption and Akt stimulation of ovarian follicles for infertility treatment (2013, background): “When Hippo signaling is disrupted, decreases in pYAP increase nuclear YAP levels (17).”
• Alternative Wnt Signaling Activates YAP/TAZ (2015, methodology): “For this purpose, we utilized active forms of YAP (YAP-5SA) and TAZ (TAZ-4SA), which are constitutively active due to mutations in the inhibitory Lats phosphorylation sites (Zhao et al., 2011).”
• Nuclear Lamin-A Scales with Tissue Stiffness and Enhances Matrix-Directed Differentiation (2013, background): “Widely expressed transcriptional regulators that include YAP1 of the Hippo pathway, which promotes growth and regeneration (17), as well as components of the serum response factor (SRF) pathway, which promote cytoskeletal gene expression in differentiation (18), exhibit low nuclear activity in cells”
• Hippo pathway effector Yap promotes cardiac regeneration (2013, background): “Hippo, Salvador, Mats, and Yorkie are structurally and functionally orthologous to mammalian Mst1/2, Sav1, Lats1/2, and Yap/Taz, respectively, and many of these mammalian Hippo signaling components have been implicated in the control of organ size and tumorigenesis (20, 21, 30, 31).”