Intestinal homeostasis is key to the maintenance of good health. The small intestine plays important roles in absorption, digestion, hormonal and immune functions. Crypt base columnar (CBC) stem cells residing at the bottom of crypts are nurtured by Paneth cells, and together create the stem cell niche, the foundation of intestinal homeostasis. CBC stem cells replicate to replenish their number, or differentiate into a variety of epithelial cells with specialized functions. Notch signaling is a cell–cell signaling pathway that regulates both the proliferation and differentiation of CBC stem cells. NOTCH1 and NOTCH2 stimulated by canonical Notch ligands DLL1 and DLL4 mediate Notch signaling in the intestine that, in concert with other signaling pathways including the WNT and BMP pathways, determines cell fates. Importantly, interactions between Notch receptors and canonical Notch ligands are regulated by O-glycans linked to Ser/Thr in epidermal growth factor-like (EGF) repeats of the Notch receptor extracellular domain (NECD). The O-glycans attached to NECD are key regulators of the strength of Notch signaling. Imbalances in Notch signaling result in altered cell fate decisions and may lead to cancer in the intestine. In this review, we summarize the impacts of mutations in Notch pathway members on intestinal development and homeostasis, with a focus on the glycosyltransferases that transfer O-glycans to EGF repeats of NOTCH1, NOTCH2, DLL1 and DLL4.
The flower represents the Drosophila testis niche with the hub cells at the center. Each petal of the flower represents Germline stem cells (GSCs) with a large and a smaller purple circle representing centromere; green rays representing stronger centromeres preferentially attach to the niche. Red and green caterpillars represent sister chromatids in prometaphase with separable old and new H3 in GSCs. Further, large butterflies closer to the flower represent prometaphase GSCs with a red wing vs a green wing representing non-overlapping old and new H3. Small orange butterflies away from the flower represent prophase gonialblast cells with overlapping old and new H3 signals. The background is from coiled sperm from the fly testis. Cover art generated by Professor Tim Phelps.
Glycans that regulate Notch signaling in the intestine
Mohd Nauman, Pamela Stanley; Glycans that regulate Notch signaling in the intestine. Biochem Soc Trans 29 April 2022; 50 (2): 689–701. doi: https://doi.org/10.1042/BST20200782
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