Proteins+in+Developement

Mouse mutants with neural tube disorders (NTDs) have been studied to identify molecular pathways in neurulation. The early studies of the Loop-tail mouse revealed //Vangl2// to be a planar cell polarity (PCP) gene causing severe NTDs in the mutant mouse. The Loop-tail mouse is a heterozygous semi-dominant mutation easily identified by a characteristic loop tail and urogenital defects. Homozygotes of this mutant die in utero of craniorachischisis, a severe form of open neural tube disorder where the neural tube fails to close from the midbrain to the tail (3). The Loop-tail mutation is caused by mutations in the //Vangl2// gene that code for a four transmembrane protein.
 * VANGL1 and VANGL2: Proteins in development **



//Vangl2// belongs to a highly conserved group of planar cell polarity proteins initially discovered in //Drosophilia//.(3) The //Vangl2// gene is the mammalian homolog of //Stbm/Vang// in //Drosophilia// (2). The //Vangl2// gene is required for establishing planar cell polarity in //Drosophilia//, developing eye, wing, and leg tissues. This study was the first to provide evidence for involvement of PCP pathway in neural tube defects in mammalians (2). //Vangl1// gene is a highly conserved paralog of //Vangl2//; it is present on mouse chromosome 3qF2.2 and human chromosome 1p13.1. //Vangl2// locus is located on mouse chromosome 1qH3 and human chromosome 1q23.2. The //Vangl1// locus has a duplicated block similar to //Vangl2// indicating a similar or overlapping role for the //Vangl2// and //Vangl1// genes (5).



Members of the planar cell polarity pathway are highly conserved in vertebrates, controlling the morphogenesis of convergent extension during gastrulation and neurulation. The //Vangl1// vertebrae homolog of //Vangl2// encodes for four membrane proteins (or 4 transmembrane domains), and a cytoplasmic domain with PDZ-binding motif that mediates protein to protein interaction (1). //Vangl2//, initially found in //Drosophilia//, include membrane proteins //Frizzled// and //Van Gogh//, and cytoplasmic proteins //Dishevelled// and //Prickle// (3). //Vangl1// and //Vangl2// have a conserved function; they bind to three mammalian //Dvl// proteins. //Dishevelled// (//Dvl//) gene encodes for a signal transduction protein that triggers planar cell polarity cascades. Therefore it can be concluded that //Vangl1// and //Vangl2// bind to //Dvl 1-2-3// and are a part of the PCP pathway in neural tube development (1). Home VANGL1 Mutations



﻿ ﻿ ﻿  ﻿1. Kibar Ph.D., Zoha, et al. “Mutations in VANGL1 Associated with Neural - Tube Defects.” //New England Journal of Medicine// 356 (Apr. 2007): 1432- 1437. Print 2.Kibar, Zoha, et al. “Novel Mutations in VANGL1 in Neural Tube Defects.” Human Mutations 30(7) (July 2009): E706-E715. Print. 3.Torban, Elena, Anne-Marie Patenaude, and Et.al. “Genetic interaction between members of the Vangl family causes neural tube defects in mice.” Proceedings of the National Academy of Sciences of the United Stats of America 105.9 (2008): 3449-3454. EBSCO Host. Web. 8 Oct. 2010. [].

5.Doudney, K., G. E. Moore, and P. Ybot-Gonzalez. “Analysis of the Planar Cell Polarity Gene Vangl2 and its Co-Expressed Paralogue Vangl1 in Neural Tube Defect Patients.” American Journal of Medical Genetics 136A (2005): 90-92. EBSCO Host. Web. 10 Oct. 2010. []