Disease relevance of Vangl2

• These findings suggest a molecular mechanism for the neural tube defect seen in Lp mice [1].
• The pattern of delayed neuropore closure in Lp/+ embryos resembles that caused by the ct and Sp mutations and is likely to be responsible for the development of tail defects (i.e., looped tails) and spina bifida in Lp/+ mice [2].
• In this study, we describe complex cardiovascular defects in Lp homozygotes, which include double-outlet right ventricle, with obligatory perimembranous ventricular septal defects, and double-sided aortic arch, with associated abnormalities in the aortic arch arteries [3].

High impact information on Vangl2

• Polarization defects in animals heterozygous for Vangl2 and Scrb1 are comparable with Vangl2 homozygotes, demonstrating genetic interactions between these genes in the regulation of PCP in mammals [4].
• Linkage studies indicate that gld is located between Pep-3 and Lp on chromosome 1 [5].
• This locus, designated Bxv-1, mapped to the same site on chromosome 1 in all strains: Id-1-Pep-3-[Bxv-1-Lp] [6].
• This review will summarize recent findings documenting the involvement of Stbm (Vangl2) and associated proteins in planar cell polarity, non-canonical Wnt signaling and convergent extension movements [7].
• Loss of Lpp1 function disrupts neurulation by permitting more extensive floor plate induction by Shh, thereby inhibiting midline bending of the neural plate during initiation of neurulation [8].

Chemical compound and disease context of Vangl2

• The effects of retinoic acid (RA) on the manifestation and nature of neural tube defects (NTD) in heterozygous embryos of mutant mice carrying the gene loop-tail (Lp) and in normal (+/+) littermates and embryos from normal homozygous matings were compared with NTD that occur in untreated abnormal homozygous (Lp/Lp) embryos [9].

Biological context of Vangl2

• Dvl2 genetically interacts with Loop-tail, a point mutation in the mammalian PCP gene Vangl2, during neurulation [10].
• Physical delineation of a 700-kb region overlapping the Looptail mutation on mouse chromosome 1 [11].
• Heterozygous Lp mice are characterized by a "looped-tail" and wobbly head movements [11].
• In the present study, we have created a high-resolution physical map of the Lp genetic interval that is based on long-range restriction mapping by PFGE, fluorescence in situ hybridization analysis of interphase nuclei and extended chromatid fibers, and the assembly of a cloned contig [11].
• Nucleotide sequencing of Nhlh1 cDNA clones from wild type (WT) and Lp/Lp embryos failed to identify sequence alterations associated with the mutant phenotype [12].

Anatomical context of Vangl2

• In epithelial cells, MAGI-3, frizzled-4, and Ltap colocalized at cell contact sites, indicating that these molecules form a physiologically significant complex [13].
• Intriguing, the Loop-tail mutation that disrupts both convergent extension in the neuroepithelium and PCP in the cochlea does not disrupt Dvl2 membrane distribution in the neuroepithelium, in contrast to its drastic effect on Dvl2 localization in the cochlea [10].
• The mouse looptail (Lp) mutation is an established model for neural tube defects with homozygous Lp embryos showing an open neural tube from the caudal midbrain to the tip of the tail [11].
• The loop-tail (Lp) mutant mouse provides a model for the most severe NTD, craniorachischisis, in which the brain and spinal cord remain open [8].
• Heterozygous Lp/+ embryos initiate neural tube closure at the cervical/hindbrain boundary with a slight delay compared with +/+ littermates [2].

Associations of Vangl2 with chemical compounds

• At the level of the hindbrain, the otocysts became displaced ventrally in abnormal (Lp/Lp) embryos, and the everted neuroepithelium showed a diminished "luminal" reaction to the lectins WGA and Con A, as compared with normal embryos [14].
• EXPERIMENTAL DESIGN: We have replaced 5-FU in the weekly combination of CPT-11, folinic acid (FA) and 5-FU chemotherapy by 5-FC and an adenoviral vector that carries the L-plastin (Lp) tumor-specific promoter-driven transcription unit encoding the cytosine deaminase gene linked to the E1A gene by an internal ribosomal entry site element [15].
• The hindbrain and spinal cord were studied by transmission electron microscopy with and without lanthanum nitrate treatment in nine-day embryos of the loop-tail (Lp) mutant mouse [16].
• Cranial effects of retinoic acid in the loop-tail (Lp) mutant mouse [9].

Other interactions of Vangl2

• The Lp gene has been mapped to a 0.6-cM interval on mouse chromosome 1 delineated by two clusters of markers, Fcer1gamma/Usf1/D1Mit113/D1Wsu1 on the proximal side and Fcer1alpha/Spna1/D1Mit149 distally [11].
• Nhlh1, a member of the basic helix-loop-helix family of transcription factors, is expressed in the developing neural tube in structures affected by the Lp mutation and has been regionally assigned to the distal part of mouse Chr 1 [12].
• The Lp interval, between D1Mit113 and Tagln2, can be spanned by two nonchimeric overlapping YACs that define a physical distance of approximately 1 Mb [17].
• Test-cross data show the following gene order and recombination percentages: Dip-1 19.0 +/- 3.8% Lp 7.4 +/- 2.2% Akp-1 [18].
• To begin to elucidate the mechanisms of PCP in vertebrates, the localization of the protein Vangl2 (Van Gogh-like) was determined during the development of the mammalian cochlea [19].

Analytical, diagnostic and therapeutic context of Vangl2

• Sequence analysis of both vertebrate and invertebrate homologs indicates that stbm has been highly conserved throughout evolution [20].
• Ultrastructural aspects of the extracellular matrix (ECM) in the midaxial region of dysraphic embryos of the loop-tail (Lp) mutant mouse were analyzed by means of electron microscopy [21].

References