PMID- 21098564
OWN - NLM
STAT- MEDLINE
DCOM- 20101221
LR  - 20211203
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Print)
IS  - 0950-1991 (Linking)
VI  - 137
IP  - 24
DP  - 2010 Dec
TI  - The Hippo tumor suppressor pathway regulates intestinal stem cell regeneration.
PG  - 4135-45
LID - 10.1242/dev.060483 [doi]
AB  - Identification of the signaling pathways that control the proliferation of stem 
      cells (SCs), and whether they act in a cell or non-cell autonomous manner, is key 
      to our understanding of tissue homeostasis and cancer. In the adult Drosophila 
      midgut, the Jun N-Terminal Kinase (JNK) pathway is activated in damaged 
      enterocyte cells (ECs) following injury. This leads to the production of Upd 
      cytokines from ECs, which in turn activate the Janus kinase (JAK)/Signal 
      transducer and activator of transcription (STAT) pathway in Intestinal SCs 
      (ISCs), stimulating their proliferation. In addition, the Hippo pathway has been 
      recently implicated in the regulation of Upd production from the ECs. Here, we 
      show that the Hippo pathway target, Yorkie (Yki), also plays a crucial and 
      cell-autonomous role in ISCs. Activation of Yki in ISCs is sufficient to increase 
      ISC proliferation, a process involving Yki target genes that promote division, 
      survival and the Upd cytokines. We further show that prior to injury, Yki 
      activity is constitutively repressed by the upstream Hippo pathway members Fat 
      and Dachsous (Ds). These findings demonstrate a cell-autonomous role for the 
      Hippo pathway in SCs, and have implications for understanding the role of this 
      pathway in tumorigenesis and cancer stem cells.
FAU - Karpowicz, Phillip
AU  - Karpowicz P
AD  - Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, 
      MA 02115, USA. pkarpowicz@genetics.med.harvard.edu
FAU - Perez, Jessica
AU  - Perez J
FAU - Perrimon, Norbert
AU  - Perrimon N
LA  - eng
GR  - P30 DK043351/DK/NIDDK NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Cadherins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (STAT Transcription Factors)
RN  - 0 (Trans-Activators)
RN  - 0 (YAP-Signaling Proteins)
RN  - 0 (Yki protein, Drosophila)
RN  - 0 (ds protein, Drosophila)
RN  - 0 (esg protein, Drosophila)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (hpo protein, Drosophila)
SB  - IM
MH  - Animals
MH  - Cadherins/genetics/metabolism
MH  - Cell Differentiation/physiology
MH  - Cell Proliferation
MH  - Drosophila
MH  - Drosophila Proteins/genetics/*metabolism
MH  - Enterocytes/cytology
MH  - Intestines/*cytology
MH  - Intracellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Microscopy, Fluorescence
MH  - Nuclear Proteins/genetics/metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - STAT Transcription Factors/genetics/metabolism
MH  - Signal Transduction/genetics/physiology
MH  - Stem Cells/*cytology/*metabolism
MH  - Temperature
MH  - Trans-Activators/genetics/metabolism
MH  - YAP-Signaling Proteins
PMC - PMC2990205
EDAT- 2010/11/26 06:00
MHDA- 2010/12/22 06:00
PMCR- 2011/06/15
CRDT- 2010/11/25 06:00
PHST- 2010/11/25 06:00 [entrez]
PHST- 2010/11/26 06:00 [pubmed]
PHST- 2010/12/22 06:00 [medline]
PHST- 2011/06/15 00:00 [pmc-release]
AID - 137/24/4135 [pii]
AID - 10.1242/dev.060483 [doi]
PST - ppublish
SO  - Development. 2010 Dec;137(24):4135-45. doi: 10.1242/dev.060483.