title: Numb modulates intestinal epithelial cells toward goblet cell phenotype by inhibiting the Notch signaling pathway.
abstract: Numb was originally identified as an important cell fate determinant that is asymmetrically inherited during mitosis and controls the fate of sibling cells by inhibiting the Notch signaling pathway in neural tissue. The small intestinal epithelium originates from the division of stem cells that reside in the crypt, which further differentiate into goblet cells, absorptive cells, paneth cells, and enteroendocrine cells. However, Numb's involvement in the differentiation process of intestinal epithelium is largely unknown. In the present study, we confirm that both the Numb mRNA and protein isoforms are expressed in adult mouse intestinal mucosa. Numb protein is ubiquitously expressed throughout the crypt-villus axis of the small intestinal epithelium and is mainly localized to the cytoplasmic membrane. Down-regulation of endogenous Numb using RNA interference in cultured intestinal LS174T cells increased Notch signaling, leading to the up-regulation of Hes1 and the down-regulation of Hath1. Knockdown of Numb alleviated MUC2 protein expression and led to loss of the goblet cell phenotype in LS174Tl cells. Our results provide the first evidence that Numb, an important cell fate determinant, modulates intestinal epithelial cells towards the goblet cell phenotype by inhibiting the Notch signaling pathway.
authors.affiliation: Department of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Yang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhu
authors.forename: Jianying
authors.initials: J
authors.lastname: Bai
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.forename: Yin
authors.initials: Y
authors.lastname: Tian
authors.forename: Xiaohuan
authors.initials: X
authors.lastname: Li
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Peng
authors.forename: Yonghong
authors.initials: Y
authors.lastname: He
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Ji
authors.forename: Wensheng
authors.initials: W
authors.lastname: Chen
authors.forename: Dianchun
authors.initials: D
authors.lastname: Fang
authors.forename: Rongquan
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D020397:Goblet Cells / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology; D008156:Luciferases / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D008156:Luciferases; D008565:Membrane Proteins; D055262:Mucin-2; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C500943:Atoh1 protein, mouse; C489734:Hes1 protein, mouse; C113026:NUMB protein, human; C106293:Numb protein, mouse