Abstract
Although a developmental role for Hippo signaling in organ size control is well appreciated, how this pathway functions in tissue regeneration is largely unknown. Here we address this issue using a dextran sodium sulfate (DSS)-induced colonic regeneration model. We find that regenerating crypts express elevated Yes-associated protein (YAP) levels. Inactivation of YAP causes no obvious intestinal defects under normal homeostasis, but severely impairs DSS-induced intestinal regeneration. Conversely, hyperactivation of YAP results in widespread early-onset polyp formation following DSS treatment. Thus, the YAP oncoprotein must be exquisitely controlled in tissue regeneration to allow compensatory proliferation and prevent the intrinsic oncogenic potential of a tissue regeneration program.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / deficiency
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Adaptor Proteins, Signal Transducing / genetics
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Adaptor Proteins, Signal Transducing / physiology*
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Animals
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Blotting, Western
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism
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Colonic Polyps / chemically induced
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Colonic Polyps / genetics
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Colonic Polyps / physiopathology
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Dextran Sulfate
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Female
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Gene Expression
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Humans
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Immunohistochemistry
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Intestinal Mucosa / metabolism
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Intestines / pathology
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Intestines / physiopathology*
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Phosphoproteins / deficiency
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Phosphoproteins / genetics
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Phosphoproteins / physiology*
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Regeneration / genetics
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Regeneration / physiology*
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / genetics
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Signal Transduction / physiology*
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YAP-Signaling Proteins
Substances
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Adaptor Proteins, Signal Transducing
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Cell Cycle Proteins
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Drosophila Proteins
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Intracellular Signaling Peptides and Proteins
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Phosphoproteins
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RNA, Messenger
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Sav1 protein, mouse
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YAP-Signaling Proteins
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Yap1 protein, mouse
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Dextran Sulfate
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Protein Serine-Threonine Kinases
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hpo protein, Drosophila