Transcription factor foxq1 controls mucin gene expression and granule content in mouse stomach surface mucous cells. Gastroenterology 2008 Aug;135(2):591-600
Date
06/19/2008Pubmed ID
18558092Pubmed Central ID
PMC2955860DOI
10.1053/j.gastro.2008.04.019Scopus ID
2-s2.0-48549090850 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
BACKGROUND & AIMS: The gastric mucosa provides a stringent epithelial barrier and produces acid and enzymes that initiate digestion. In this regenerating tissue, progenitors differentiate continually into 4 principal specialized cell types, yet underlying mechanisms of differentiation are poorly understood. We identified stomach-restricted expression of the forkhead transcription factor FOXQ1.
METHODS: We used a combination of genetic, histochemical, ultrastructural, and molecular analysis to study gastric cell lineages with respect to FOXQ1.
RESULTS: Within the developing and adult gastrointestinal tract, Foxq1 messenger RNA (mRNA) is restricted to the stomach and expressed predominantly in foveolar (pit) cells, the abundant mucin-producing cells that line the mucosal surface. Mice carrying Foxq1 coding mutations show virtual absence of mRNA and protein for the backbone of the major stomach mucin MUC5AC. These observations correspond to a paucity of foveolar cell secretory vesicles and notable loss of stomach but not intestinal mucus. Transcriptional profiling identified a surprisingly restricted set of genes with altered expression in Foxq1 mutant stomachs. MUC5AC is a highly tissue-restricted product that similarly depends on FOXQ1 in its other major site of expression, conjunctival goblet cells.
CONCLUSIONS: Taken together, these observations imply that promotion of gastric MUC5AC synthesis is a primary, cell-autonomous function of FOXQ1. This study is the first to implicate a transcription factor in terminal differentiation of foveolar cells and begins to define the requirements to assemble highly specialized organelles and cells in the gastric mucosa.
Author List
Verzi MP, Khan AH, Ito S, Shivdasani RAMESH terms used to index this publication - Major topics in bold
AnimalsBase Sequence
Cell Differentiation
Cell Lineage
Conjunctiva
Epithelial Cells
Forkhead Transcription Factors
Gastric Mucosa
Gene Expression Profiling
Gene Expression Regulation
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Molecular Sequence Data
Mucin 5AC
Mucins
Mutation
RNA, Messenger
Secretory Vesicles
Transcription, Genetic
Ultrasonography