Stem cell regulation by the Hippo pathway

Background: The Hippo pathway coordinates cell proliferation, apoptosis, and differentiation, and has emerged as a major regulator of organ development and regeneration. Central to the mammalian Hippo pathway is the action of the transcriptional regulators TAZ (also known as WWTR1) and YAP, which are controlled by a kinase cascade that is sensitive to mechanosensory and cell polarity cues.

Scope of review: We review recent studies focused on the Hippo pathway in embryonic and somatic stem cell renewal and differentiation.

Major conclusions: Accurate control of TAZ and YAP is crucial for the self-renewal of stem cells and in guiding distinct cell fate decisions. In vivo studies have implicated YAP as a key regulator of tissue-specific progenitor cell proliferation and tissue regeneration. Misappropriate activation of nuclear TAZ and YAP transcriptional activity drives tissue overgrowth and is implicated in cancer stem cell-like properties that promote tumor initiation.

General significance: Understanding the activity and regulation of Hippo pathway effectors will offer insight into human pathologies that evolve from the deregulation of stem cell populations. Given the roles of the Hippo pathway in directing cell fate and tissue regeneration, the discernment of Hippo pathway regulatory cues will be essential for the advancement of regenerative medicine. This article is part of a Special Issue entitled Biochemistry of Stem Cells.