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Notch signaling regulates proliferation and differentiation in the adult mouse intestine (899.4)
Author(s) -
Zayan Nichole,
Carulli Alexis,
Samuelson Linda
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.899.4
Subject(s) - notch signaling pathway , enterocyte , notch 1 , biology , population , hes1 , microbiology and biotechnology , endocrinology , cell growth , alkaline phosphatase , medicine , small intestine , cancer research , signal transduction , biochemistry , enzyme , environmental health
Human gastrointestinal tumors can exhibit increased Notch signaling; accordingly, intestinal Notch over‐activation was examined in genetic mouse models ubiquitously expressing the Notch intracellular domain (NICD) in the intestinal epithelium. Based on previous studies, we hypothesized that Notch over‐activation would induce increased proliferation, decreased secretory cells, and increased absorptive cell numbers. NICD expression was activated in bitransgenic mice (Villin‐CreERT2 ; Rosa‐FSF‐NICD‐nGFP) by 5 daily doses of tamoxifen with intestine collected on day 6. We found that epithelial proliferation was increased and the goblet cell population was decreased in the NICD intestine. However, contrary to our hypothesis, the alkaline phosphatase‐positive enterocyte population appeared decreased, which was confirmed by reduced mRNA levels of the enterocyte marker sucrase‐isomaltase. Based on these data, we concluded that Notch over‐activation increases proliferation and decreases all differentiated cell types, not just secretory cells. This finding suggests that constitutive Notch activation in the intestine leads to a hyperproliferative state, consistent with activation of this pathway in human tumors. Grant Funding Source : Supported by APS Fellowship (NEZ) and NIH grants R01‐DK078927 (LCS) and F30‐DK095517 (AJC).