PMID- 21965616
OWN - NLM
STAT- MEDLINE
DCOM- 20111227
LR  - 20111012
IS  - 1477-9129 (Electronic)
IS  - 0950-1991 (Linking)
VI  - 138
IP  - 21
DP  - 2011 Nov
TI  - Distinct levels of Notch activity for commitment and terminal differentiation of 
      stem cells in the adult fly intestine.
PG  - 4585-95
LID - 10.1242/dev.065292 [doi]
AB  - Tight regulation of self-renewal and differentiation of adult stem cells ensures 
      that tissues are properly maintained. In the Drosophila intestine, both 
      commitment, i.e. exit from self-renewal, and terminal differentiation are 
      controlled by Notch signaling. Here, we show that distinct requirements for Notch 
      activity exist: commitment requires high Notch activity, whereas terminal 
      differentiation can occur with lower Notch activity. We identified the gene 
      GDP-mannose 4,6-dehydratase (Gmd), a modulator of Notch signaling, as being 
      required for commitment but dispensable for terminal differentiation. Gmd loss 
      resulted in aberrant, self-renewing stem cell divisions that generated extra 
      ISC-like cells defective in Notch reporter activation, as well as wild-type-like 
      cell divisions that produced properly terminally differentiated cells. Lowering 
      Notch signaling using additional genetic means, we provided further evidence that 
      commitment has a higher Notch signaling requirement than terminal 
      differentiation. Our work suggests that a commitment requirement for high-level 
      Notch activity safeguards the stem cells from loss through differentiation, 
      revealing a novel role for the importance of Notch signaling levels in this 
      system.
FAU - Perdigoto, Carolina N
AU  - Perdigoto CN
AD  - Institut Pasteur, Developmental Biology Department, F-75015 Paris, France.
FAU - Schweisguth, Francois
AU  - Schweisguth F
FAU - Bardin, Allison J
AU  - Bardin AJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110928
PL  - England
TA  - Development
JT  - Development (Cambridge, England)
JID - 8701744
RN  - 0 (Drosophila Proteins)
RN  - 0 (Receptors, Notch)
RN  - EC 2.4.1.- (Fucosyltransferases)
RN  - EC 2.4.1.221 (O-fucosyltransferase 1, Drosophila)
RN  - EC 4.2.1.- (Hydro-Lyases)
SB  - IM
MH  - Animals
MH  - Cell Differentiation/*physiology
MH  - Drosophila Proteins/genetics/metabolism
MH  - Drosophila melanogaster/*anatomy & histology/*physiology
MH  - Fucosyltransferases/genetics/metabolism
MH  - Genes, Reporter
MH  - Hydro-Lyases/genetics/metabolism
MH  - Intestines/*cytology/physiology
MH  - Mutation
MH  - Receptors, Notch/genetics/*metabolism
MH  - Signal Transduction/physiology
MH  - Stem Cells/cytology/*physiology
EDAT- 2011/10/04 06:00
MHDA- 2011/12/28 06:00
CRDT- 2011/10/04 06:00
PHST- 2011/10/04 06:00 [entrez]
PHST- 2011/10/04 06:00 [pubmed]
PHST- 2011/12/28 06:00 [medline]
AID - dev.065292 [pii]
AID - 10.1242/dev.065292 [doi]
PST - ppublish
SO  - Development. 2011 Nov;138(21):4585-95. doi: 10.1242/dev.065292. Epub 2011 Sep 28.