PMID- 22388892
OWN - NLM
STAT- MEDLINE
DCOM- 20120607
LR  - 20240610
IS  - 1476-4679 (Electronic)
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 14
IP  - 4
DP  - 2012 Mar 4
TI  - Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB 
      signalling.
PG  - 401-8
LID - 10.1038/ncb2464 [doi]
AB  - Maintenance of adult tissues is carried out by stem cells and is sustained 
      throughout life in a highly ordered manner. Homeostasis within the stem-cell 
      compartment is governed by positive- and negative-feedback regulation of 
      instructive extrinsic and intrinsic signals. ErbB signalling is a prerequisite 
      for maintenance of the intestinal epithelium following injury and tumour 
      formation. As ErbB-family ligands and receptors are highly expressed within the 
      stem-cell niche, we hypothesize that strong endogenous regulators must control 
      the pathway in the stem-cell compartment. Here we show that Lrig1, a 
      negative-feedback regulator of the ErbB receptor family, is highly expressed by 
      intestinal stem cells and controls the size of the intestinal stem-cell niche by 
      regulating the amplitude of growth-factor signalling. Intestinal stem-cell 
      maintenance has so far been attributed to a combination of Wnt and Notch 
      activation and Bmpr inhibition. Our findings reveal ErbB activation as a strong 
      inductive signal for stem-cell proliferation. This has implications for our 
      understanding of ErbB signalling in tissue development and maintenance and the 
      progression of malignant disease.
FAU - Wong, Vivian W Y
AU  - Wong VW
AD  - The Anne McLaren Laboratory for Regenerative Medicine, University of Cambridge, 
      Cambridge CB2 0SZ, UK.
FAU - Stange, Daniel E
AU  - Stange DE
FAU - Page, Mahalia E
AU  - Page ME
FAU - Buczacki, Simon
AU  - Buczacki S
FAU - Wabik, Agnieszka
AU  - Wabik A
FAU - Itami, Satoshi
AU  - Itami S
FAU - van de Wetering, Marc
AU  - van de Wetering M
FAU - Poulsom, Richard
AU  - Poulsom R
FAU - Wright, Nicholas A
AU  - Wright NA
FAU - Trotter, Matthew W B
AU  - Trotter MW
FAU - Watt, Fiona M
AU  - Watt FM
FAU - Winton, Doug J
AU  - Winton DJ
FAU - Clevers, Hans
AU  - Clevers H
FAU - Jensen, Kim B
AU  - Jensen KB
LA  - eng
GR  - 17044/CRUK_/Cancer Research UK/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - G0800784/MRC_/Medical Research Council/United Kingdom
GR  - 088454/WT_/Wellcome Trust/United Kingdom
GR  - 079249/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120304
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Lrig1 protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
SB  - IM
MH  - Animals
MH  - Feedback, Physiological
MH  - Gene Expression Profiling
MH  - Genes, erbB
MH  - *Homeostasis
MH  - Intestines/*cytology/pathology
MH  - Membrane Glycoproteins/deficiency/*metabolism
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Mice, Knockout
MH  - Nerve Tissue Proteins/deficiency/*metabolism
MH  - Receptor, ErbB-2/antagonists & inhibitors/*metabolism
MH  - *Signal Transduction
MH  - Stem Cell Niche
MH  - Stem Cells/*cytology/*metabolism
PMC - PMC3378643
MID - UKMS41101
OID - NLM: UKMS41101
EDAT- 2012/03/06 06:00
MHDA- 2012/06/08 06:00
PMCR- 2012/10/01
CRDT- 2012/03/06 06:00
PHST- 2011/11/03 00:00 [received]
PHST- 2012/02/13 00:00 [accepted]
PHST- 2012/03/06 06:00 [entrez]
PHST- 2012/03/06 06:00 [pubmed]
PHST- 2012/06/08 06:00 [medline]
PHST- 2012/10/01 00:00 [pmc-release]
AID - ncb2464 [pii]
AID - 10.1038/ncb2464 [doi]
PST - epublish
SO  - Nat Cell Biol. 2012 Mar 4;14(4):401-8. doi: 10.1038/ncb2464.