TheO-fucose glycan in the ligand-binding domain of Notch1 regulates embryogenesis and T cell development
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Open Access
- 5 February 2008
- journal article
- Published by National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 105 (5) , 1539-1544
Abstract
Mechanisms by which the extracellular domain of Notch1 controls Notch1 signaling are not well defined. Here, we show that theO-fucose glycan in the Notch1 ligand-binding domain regulates the strength of Notch1 signaling during embryogenesis, postweaning growth, and T cell development in the mouse. Heterozygotes carrying aNotch112fallele and an inactiveNotch1allele die at approximately embryonic day (E)12 with a typicalNotch1null phenotype. HomozygousNotch112f/12fmice are viable and fertile but grow somewhat more slowly than littermates after weaning.Notch112f/12fthymocytes bind less Delta1 and exhibit reduced Notch1 signaling. The number of double-positive (DP) and single-positive (SP) T cells are decreased inNotch112f/12fthymus, and DP T cells are more apoptotic. By contrast, proportionately more SP cells have matured, and SP-to-DP ratios are increased in mutant thymus. Thus, theO-fucose glycan in EGF12 of mouse Notch1 is required for optimal Notch1 signaling and T cell development in mammals.Keywords
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