Disease relevance of Vil1

• Expression and localization of villin, fimbrin, and myosin I in differentiating mouse F9 teratocarcinoma cells [1].
• Areas of metaplasia within the G-/- mouse stomach showed decreased RUNX3 expression with elevated MUC2 and villin expression [2].
• Here, we studied the role of villin during infection by Shigella flexneri, the causative agent of bacillary dysentery [3].
• We further investigated villin property to initiate actin remodeling in cellular processes such as hepatocyte growth factor-induced motility, morphogenesis, and bacterial infection [4].
• We report here that villin is induced during differentiation of aggregates of the mouse embryonal carcinoma F9, an in vitro system widely used to study extraembryonic endoderm differentiation [5].

High impact information on Vil1

• METHODS: This study presents transgenic mice that express K-ras(V12G), the most frequent oncogenic mutation in human tumors, under control of the murine villin promoter in epithelial cells of the large and small intestine [6].
• Villin, a tissue-specific, actin-binding protein of the brush border, was expressed in the two cell types [7].
• CONCLUSIONS: The presence of villin and the absence of vimentin in M cells support the intestinal origin of M cells [7].
• Cytosolic distribution of villin in M cells from mouse Peyer's patches correlates with the absence of a brush border [7].
• These results suggest that in vivo, villin is not necessary for the bundling of F-actin microfilaments, whereas it is necessary for the reorganization elicited by various signals [8].

Biological context of Vil1

• The tightly linked Vil marker can now be used as an entry point in recombinant genomic DNA libraries to clone sequences overlapping Bcg [9].
• We have developed eight new highly polymorphic markers (simple sequence repeats) corresponding to cloned genes (Vil, Inha, Des), microdissected chromosome 1 anonymous probes (lambda Mm1C136, lambda Mm1C163, lambda Mm1C165), or novel DNA markers from the region obtained by chromosome walking (D1Mcg101 and D1Mcg105) [10].
• Comparative analysis of neutral endopeptidase (NEP) and villin gene expression during mouse embryogenesis and enterocyte maturation [11].
• Developmental regulation of villin gene expression in the epithelial cell lineages of mouse digestive and urogenital tracts [12].
• Thus villin expression can be considered as an early marker of the endodermal cell lineage during the development of the digestive system [12].

Anatomical context of Vil1

• In 17-day-old embryos, a transient elevation of villin mRNA occurred just prior to a dramatic increase in microvilli length and density [11].
• In this study, cRNA probes were hybridized in situ to investigate the expression of NEP and villin genes in embryo and adult mouse enterocytes [11].
• We show that the ontogeny of villin expression is limited to the epithelial cell lineages of the digestive and uro-genital tracts and accounts for the tissue-specific expression observed in adult mice [12].
• During the development of the primitive gut, villin is faintly and discontinuously expressed in the invaginating foregut but it is expressed in every cell bordering the hindgut pocket [12].
• Conversely, during the development of the excretory and genital system, villin is only expressed after the mesenchyme/epithelium conversion following the appearance of tubular structures [12].

Associations of Vil1 with chemical compounds

• Localization of protease nexin-1 gene Spi4 between villin and acetylcholine receptor gamma genes on mouse Chromosome 1 [13].
• In wild-type animals, isolated brush borders were disrupted by the addition of Ca(2+), whereas Ca(2+) had no effect in villin-null isolates [8].
• Oral administration of dextran sulfate sodium, an agent that causes colonic epithelial injury, induced large mucosal lesions resulting in a higher death probability in mice lacking villin, 36 +/- 9.6%, compared with wild-type mice, 70 +/- 8.8%, at day 13 [8].
• These villin gene localizations add a fourth locus to the conserved gene cluster encoding the fast skeletal muscle isoform of the myosin light chain, isocitrate dehydrogenase, and the gamma crystallins and confirm the partial homology of the human chromosome 2 long arm and mouse chromosome 1 [14].
• To genetically assess the role of c-Myc during development and homeostasis of the mammalian intestine we induced deletion of the c-myc(flox) allele in the villi and intestinal stem cell-bearing crypts of juvenile and adult mice, via tamoxifen-induced activation of the CreER(T2) recombinase, driven by the villin promoter [15].

Regulatory relationships of Vil1

• Villin enhances hepatocyte growth factor-induced actin cytoskeleton remodeling in epithelial cells [16].
• Villin is coexpressed with F-actin and with alpha-foetoprotein, in most of the visceral endoderm-like cells lining the aggregates [5].

Other interactions of Vil1

• The 16/207 recombinants observed between Lsh/Vil and Cryg provide an estimated recombination frequency of 0.077 +/- 0.019, equivalent to a map distance of 7.7 +/- 1.9 cM [17].
• The proximal deletion breakpoint maps within the 0.8-cM segment separating Tp1 and Vil [18].
• The minimum size of the Spr deletion would therefore be limited to 14 cM, the genetic distance between Vil and Akp-3 [18].
• An additional 47 backcross progeny from a cross between C57BL/10ScSn and B10.L-Lshr/s mice were examined for the cosegregation of Myl-1 and Vil RFLPs with Lsh phenotypic differences [19].
• In the future, regulatory elements of the villin gene may be used to target the early expression of oncogenes to the digestive and urogenital tracts of transgenic mice [12].

Analytical, diagnostic and therapeutic context of Vil1

• Confocal microscopy localized villin at Day 4 to the apical surface and by Day 6 to the basolateral surfaces as well [1].
• In situ hybridization experiments on human chromosomes with tritiated probe allowed the regional localization of the villin locus to chromosome 2 at q35-36 [14].
• We conclude that this in vivo perfusion method is suitable for studying the absorption/secretion of electrolytes in the mouse intestine and that a lack of villin does not significantly alter basal and secretagogue-stimulated electrolyte movements across the epithelium of the mouse jejunum in vivo [20].
• Physical mapping by pulsed-field gel electrophoresis revealed that NRAMP1 is tightly linked to the villin gene and that the genomic organization (gene order and presence of CpG islands) of the chromosomal region carrying NRAMP1 is well conserved between the chicken and mammalian genomes [21].
• METHODS: The localization of cytokeratins, vimentin, and villin was determined on mouse FAE using immunocytochemistry and electron microscopy [7].

References