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Review
. 2012 Jul;22(7):339-46.
doi: 10.1016/j.tcb.2012.04.006. Epub 2012 May 31.

The Hippo signaling pathway and stem cell biology

Azucena Ramos  1 , Fernando D Camargo
Affiliations
Review

The Hippo signaling pathway and stem cell biology

Azucena Ramos et al. Trends Cell Biol. 2012 Jul.

Abstract

Stem cell (SC) activity fluctuates throughout an organism's lifetime to maintain homeostatic conditions in all tissues. As animals develop and age, their organs must remodel and regenerate themselves in response to environmental and physiological demands. Recently, the highly conserved Hippo signaling pathway, discovered in Drosophila melanogaster, has been implicated as a key regulator of organ size control across species. Deregulation is associated with substantial overgrowth phenotypes and eventual onset of cancer in various tissues. Importantly, emerging evidence suggests that the Hippo pathway can modulate its effects on tissue size by the direct regulation of SC proliferation and maintenance. These findings provide an attractive model for how this pathway might communicate physiological needs for growth to tissue-specific SC pools. In this review, we summarize the current and emerging data linking Hippo signaling to SC function.

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Figures

Figure 1
Figure 1
A schematic model of the Hippo signaling cascade in mammals. Cells, in blue with a dark blue lipid bilayer and a green nucleus, are shown with their respective cellular junctions. Blunted and arrowed lines indicate either inhibition or activation, respectively. Solid lines represent known interactions while dashed lines indicate unknown mechanisms. Crumbs (Crb), Expanded homologues (Ex1/2), Kibra, and Ajuba (Ajub) represent other potential regulators of Hippo signaling in mammals not discussed in the text.
Figure 2
Figure 2
YAP expression in stem/progenitor cell compartments. (A) Intestinal crypt architecture with quiescent (+4) and active crypt base columnar (CBC, Lgr5+) stem cells shown. Also shown but not discussed in the text are mature cell types, the transit-amplifying compartment, and components of the intestinal stroma (myofibroblasts). Inset depicts YAP localization in crypts, in wildtype intestine. (B) Epidermal architecture with progenitor cells residing in the basal layer (BL). Asymmetric divisions in this compartment produces short-lived progenitor cells that stratify as they differentiate, leaving the basal layer and moving up into the spinous layer (SL), granular layer (GL), and stratum corneum (SC). Inset depicts significant YAP localization in the basal layer of wildtype skin. Black dotted line represents the border between the dermis and epidermis.
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