title: Dynamic expansion of gastric mucosal doublecortin-like kinase 1-expressing cells in response to parietal cell loss is regulated by gastrin.
abstract: Doublecortin-like kinase 1 (Dclk1) is considered a reliable marker for tuft cells in the gastrointestinal tract. We investigated the dynamic changes of tuft cells associated with mouse models of oxyntic atrophy and metaplasia in the stomach. Increases in the numbers of Dclk1-positive tuft cells were observed in several models of parietal cell loss. However, the expanded population of Dclk1-expressing cells showed a morphologically distinct structure in apical microvilli and acetylated microtubules, which was not seen in the tuft cells present in the normal gastric mucosa. These microvillar sensory cells (MVSCs) showed no evidence of proliferation. The expansion of the MVSCs induced by oxyntic atrophy was reversible after the return of parietal cells. More important, expansion of MVSCs after induced parietal cell loss was not observed in Gast(-/-) mice. Although the Dclk1-expressing cells in the normal gastric mucosa were in part derived from Lrig1-expressing stem cells, the Lrig1-lineaged cells did not produce the expanded Dclk1-expressing cells associated with oxyntic atrophy. These studies indicate that loss of parietal cells leads to the reversible emergence of a novel Dclk1-expressing sensory cell population in the gastric mucosa.
authors.affiliation: Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Nashville VA Medical Center, Nashville, Tennessee.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Choi
authors.affiliation: Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Christine P
authors.initials: CP
authors.lastname: Petersen
authors.affiliation: Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Lynne A
authors.initials: LA
authors.lastname: Lapierre
authors.affiliation: Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Janice A
authors.initials: JA
authors.lastname: Williams
authors.affiliation: Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee.
authors.forename: Victoria G
authors.initials: VG
authors.lastname: Weis
authors.affiliation: Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee; Epithelial Biology Center, Vanderbilt University School of Medicine, Nashville, Tennessee; Nashville VA Medical Center, Nashville, Tennessee; Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee; Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee. Electronic address: jim.goldenring@vanderbilt.edu.
authors.forename: James R
authors.initials: JR
authors.lastname: Goldenring
authors.affiliation: Section of Surgical Sciences, Vanderbilt University School of Medicine, Nashville, Tennessee; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Republic of Korea; Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: kitaek@yuhs.ac.
authors.forename: Ki Taek
authors.initials: KT
authors.lastname: Nam
mesh_terms: D000818:Animals; D001284:Atrophy / Q000378:metabolism / Q000473:pathology; D000089742:Doublecortin-Like Kinases; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D005755:Gastrins / Q000378:metabolism*; D008679:Metaplasia; D051379:Mice; D010295:Parietal Cells, Gastric / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D013270:Stomach / Q000473:pathology
chemical_list: D005755:Gastrins; D000089742:Doublecortin-Like Kinases; C485525:Dclk1 protein, mouse; D017346:Protein Serine-Threonine Kinases