title: Distinct levels of Notch activity for commitment and terminal differentiation of stem cells in the adult fly intestine.
abstract: 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.
authors.affiliation: Institut Pasteur, Developmental Biology Department, F-75015 Paris, France.
authors.forename: Carolina N
authors.initials: CN
authors.lastname: Perdigoto
authors.forename: Francois
authors.initials: F
authors.lastname: Schweisguth
authors.forename: Allison J
authors.initials: AJ
authors.lastname: Bardin
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000033:anatomy & histology* / Q000502:physiology*; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D017930:Genes, Reporter; D006836:Hydro-Lyases / Q000235:genetics / Q000378:metabolism; D007422:Intestines / Q000166:cytology* / Q000502:physiology; D009154:Mutation; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D051880:Receptors, Notch; D005647:Fucosyltransferases; C471275:O-fucosyltransferase 1, Drosophila; D006836:Hydro-Lyases