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The gastric epithelial progenitor cell niche and differentiation of the zymogenic (chief) cell lineage.
- Source :
-
Developmental biology [Dev Biol] 2009 Jan 01; Vol. 325 (1), pp. 211-24. Date of Electronic Publication: 2008 Oct 31. - Publication Year :
- 2009
-
Abstract
- In the mammalian gastrointestinal tract, the cell fate decisions that specify the development of multiple, diverse lineages are governed in large part by interactions of stem and early lineage progenitor cells with their microenvironment, or niche. Here, we show that the gastric parietal cell (PC) is a key cellular component of the previously undescribed niche for the gastric epithelial neck cell, the progenitor of the digestive enzyme secreting zymogenic (chief) cell (ZC). Genetic ablation of PCs led to failed patterning of the entire zymogenic lineage: progenitors showed premature expression of differentiated cell markers, and fully differentiated ZCs failed to develop. We developed a separate mouse model in which PCs localized not only to the progenitor niche, but also ectopically to the gastric unit base, which is normally occupied by terminally differentiated ZCs. Surprisingly, these mislocalized PCs did not maintain adjacent zymogenic lineage cells in the progenitor state, demonstrating that PCs, though necessary, are not sufficient to define the progenitor niche. We induced this PC mislocalization by knocking out the cytoskeleton-regulating gene Cd2ap in Mist1(-/-) mice, which led to aberrant E-cadherin localization in ZCs, irregular ZC-ZC junctions, and disruption of the ZC monolayer by PCs. Thus, the characteristic histology of the gastric unit, with PCs in the middle and ZCs in the base, may depend on establishment of an ordered adherens junction network in ZCs as they migrate into the base.
- Subjects :
- Adaptor Proteins, Signal Transducing deficiency
Adaptor Proteins, Signal Transducing metabolism
Animals
Basic Helix-Loop-Helix Transcription Factors deficiency
Basic Helix-Loop-Helix Transcription Factors metabolism
Cadherins metabolism
Cell Polarity
Cell Proliferation
Chief Cells, Gastric metabolism
Chief Cells, Gastric ultrastructure
Cytoskeletal Proteins deficiency
Cytoskeletal Proteins metabolism
Epithelial Cells metabolism
Epithelial Cells ultrastructure
Intercellular Junctions metabolism
Intercellular Junctions ultrastructure
Mice
Models, Biological
Parietal Cells, Gastric cytology
Parietal Cells, Gastric metabolism
Parietal Cells, Gastric ultrastructure
Protein Binding
Protein Transport
Stem Cell Niche metabolism
Stem Cell Niche ultrastructure
Stem Cells metabolism
Stem Cells ultrastructure
Cell Differentiation
Cell Lineage
Chief Cells, Gastric cytology
Epithelial Cells cytology
Stem Cell Niche cytology
Stem Cells cytology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-564X
- Volume :
- 325
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Developmental biology
- Publication Type :
- Academic Journal
- Accession number :
- 19013146
- Full Text :
- https://doi.org/10.1016/j.ydbio.2008.10.025