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The stomach mesenchymal transcription factor Barx1 specifies gastric epithelial identity through inhibition of transient Wnt signaling.
- Source :
-
Developmental cell [Dev Cell] 2005 Apr; Vol. 8 (4), pp. 611-22. - Publication Year :
- 2005
-
Abstract
- Inductive interactions between gut endoderm and the underlying mesenchyme pattern the developing digestive tract into regions with specific morphology and functions. The molecular mechanisms behind these interactions are largely unknown. Expression of the conserved homeobox gene Barx1 is restricted to the stomach mesenchyme during gut organogenesis. Using recombinant tissue cultures, we show that Barx1 loss in the mesenchyme prevents stomach epithelial differentiation of overlying endoderm and induces intestine-specific genes instead. Additionally, Barx1 null mouse embryos show visceral homeosis, with intestinal gene expression within a highly disorganized gastric epithelium. Barx1 directs mesenchymal cell expression of two secreted Wnt antagonists, sFRP1 and sFRP2, and these factors are sufficient replacements for Barx1 function. Canonical Wnt signaling is prominent in the prospective gastric endoderm prior to epithelial differentiation, and its inhibition by Barx1-dependent signaling permits development of stomach-specific epithelium. These results define a transcriptional and signaling pathway of inductive cell interactions in vertebrate organogenesis.
- Subjects :
- Animals
Gastric Mucosa embryology
Gene Expression Profiling
Gene Expression Regulation, Developmental
Gene Targeting
Homeodomain Proteins genetics
Humans
Intestines anatomy & histology
Intestines embryology
Intestines physiology
Mice
Mice, Knockout
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Tissue Culture Techniques
Transcription Factors genetics
Wnt Proteins
Gastric Mucosa metabolism
Homeodomain Proteins metabolism
Intercellular Signaling Peptides and Proteins metabolism
Mesoderm metabolism
Morphogenesis
Signal Transduction physiology
Stomach anatomy & histology
Stomach embryology
Stomach physiology
Transcription Factors metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1534-5807
- Volume :
- 8
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 15809042
- Full Text :
- https://doi.org/10.1016/j.devcel.2005.01.015