The Hippo Superhighway: Signaling Crossroads Converging on the Hippo/Yap Pathway in Stem Cells and Development

Curr Opin Cell Biol. 2013 Apr;25(2):247-53. doi: 10.1016/ Epub 2013 Jan 10.


Tissue regeneration is vital to the form and function of an organ. At the core of an organs' ability to self-renew is the stem cell, which maintains homeostasis, and repopulates injured or aged tissue. Tissue damage can dramatically change the dimensions of an organ, and during regeneration, an organ must halt growth once the original tissue dimensions have been restored. Therefore, stem cells must give rise to the appropriate number of differentiated progeny to achieve homeostasis. How this tissue-size checkpoint is regulated and how tissue size information relayed to stem cell compartments is unclear, however, it is likely that these mechanisms are altered during the course of tumorigenesis. An emerging signaling cascade, the Hippo Signaling Pathway, is a broadly conserved potent organ size regulator [1]. However, this pathway does not act alone. A number of examples demonstrate crosstalk between Hippo and other signaling pathways including Wnt, Tgfβ and Notch, with implications for stem cell biology. Here, we focus on these interactions primarily in the context of well characterized stem cell populations.

Publication types

  • Review

MeSH terms

  • Animals
  • Drosophila Proteins / metabolism
  • Embryonic Development
  • Epidermal Cells
  • Humans
  • Intestines / cytology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Neoplastic Stem Cells / metabolism
  • Nuclear Proteins / metabolism
  • Organ Size
  • Protein-Serine-Threonine Kinases / metabolism*
  • Signal Transduction*
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Stem Cells / pathology
  • Trans-Activators / metabolism
  • Wnt Proteins / metabolism


  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • Trans-Activators
  • Wnt Proteins
  • Yki protein, Drosophila
  • Protein-Serine-Threonine Kinases