The mechanisms that regulate mammalian organ size are poorly understood. It is 
unclear whether the pathways that control organ size also impinge on 
stem/progenitor cells. A highly expressed gene in stem cells is YAP1, the 
ortholog of Drosophila Yorkie, a downstream component of the Hippo pathway. 
Mutations in components of this pathway produce tissue overgrowth phenotypes in 
the fly whereas mammalian orthologs, like salvador, merlin, LATS, and YAP1, have 
been implicated in tumorigenesis. We report here that YAP1 increases organ size 
and causes aberrant tissue expansion in mice. YAP1 activation reversibly 
increases liver size more than 4-fold. In the intestine, expression of 
endogenous YAP1 is restricted to the progenitor/stem cell compartment, and 
activation of YAP1 expands multipotent undifferentiated progenitor cells, which 
differentiate upon cessation of YAP1 expression. YAP1 stimulates Notch 
signaling, and administration of gamma-secretase inhibitors suppressed the 
intestinal dysplasia caused by YAP1. Human colorectal cancers expressing higher 
levels of YAP1 share molecular aspects with YAP1-induced dysplastic growth in 
the mouse. Our data show that the Hippo signaling pathway regulates organ size 
in mammals and can act on stem cell compartments, indicating a potential link 
between stem/progenitor cells, organ size, and cancer.