Hippo signaling in mammalian stem cells

Over the past decade, the Hippo signaling cascade has been linked to organ size regulation in mammals. Indeed, modulation of the Hippo pathway can have potent effects on cellular proliferation and/or apoptosis and a deregulation of the pathway often leads to tumor development. Importantly, emerging evidence indicates that the Hippo pathway can modulate its effects on tissue size by the regulation of stem and progenitor cell activity. This role has recently been associated with the central position of the pathway in sensing spatiotemporal or mechanical cues, and translating them into specific cellular outputs. These results provide an attractive model for how the Hippo cascade might sense and transduce cellular ‘neighborhood’ cues into activation of tissue-specific stem or progenitors cells. A further understanding of this process could allow the development of new therapies for various degenerative diseases and cancers. Here, we review current and emerging data linking Hippo signaling to progenitor cell function.

► The Hippo signaling is a highly conserved signaling pathway regulating organ size.
► Components of the pathway are selectively expressed in stem and progenitor cells.
► Manipulation of the Hippo pathway results in changes in progenitor/stem cell pool size.
► Deregulation of Hippo signaling in somatic cell compartments leads to tumorigenesis.