Villin: A marker for development of the epithelial pyloric border

Abstract

In the adult gastrointestinal tract, the morphologic borders between esophagus and stomach and between stomach and small intestine are literally one cell thick. The patterning mechanisms that underlie the development of these sharp regional divisions from a once continuous endodermal tube are still obscure. In the embryonic endoderm of the developing gut, region-specific expression of certain genes (e.g., intestine-specific expression of the actin bundling protein villin) can be detected as early as 9.0 days post coitum, although the morphologic differentiation of the gut epithelium proper does not begin until 4 to 5 days later. By using a mouse model in which a ␤-galactosidase marker has been inserted into the endogenous villin locus, we examined the development of the stomach/ intestinal (pyloric) border during gut organogenesis. The data indicate that the border is not sharp from the outset. Rather, the initial border region is characterized by a decreasing gradient of villin/␤-galactosidase expression that extends into the distal stomach. A sharp epithelial border of villin/␤-galactosidase expression appears abruptly at day 16 and is further refined over the next 3 weeks to form the distinct onecell-thick border characteristic of the adult. These results indicate that an important previously unrecognized patterning event occurs in the gut epithelium at 16 days; this event may define an epithelial compartment boundary between the stomach and the intestine. The villin/ ␤-galactosidase mouse model characterized here provides an excellent substrate with which to further dissect the mechanisms involved in this patterning process.

Insig Proteins Mediate Feedback Inhibition of Cholesterol Synthesis in the Intestine

“…Mice with floxed Insig1 alleles and germ line deletion of Insig2 (Insig1 f/f ;Insig2 Ϫ/Ϫ ) were bred to Vil-Cre transgenic mice in which the Cre recombinase is driven from the gut-selective Villin promoter (27). The Vil-Cre-mediated deletion of Insig1, in combination with the germ line deletion of Insig2, rendered the resulting Insig1…”

Obligatory role for phospholipase C-γ1 in villin-induced epithelial cell migration

“…Villin also appears as an early marker of the endodermal cell lineage and a marker of cells arising from mesenchymal/epithelial conversion in the developing intestine and kidney (4,32). Thus villin and PLC-␥ 1 expression are maintained during periods of most substantial cell migration.…”

The non-muscle-myosin-II heavy chain Myh9 mediates colitis-induced epithelium injury by restricting Lgr5+ stem cells

“…However, we did not obtain the complete Myh9-knockout mouse. It could be due to the early expression of Villin-Cre in the visceral endoderm of E6.5 embryos 16 , and Myh9 ablation leads to severe defects in the visceral endoderm of E6.5 embryos 17 . Myh9 fl/ þ ; Villin-cre mice exhibited no obvious abnormality in intestinal or colonic epithelium homeostasis ( Supplementary Fig.…”