XB-ART-57271
Cells
2019 Oct 04;810:. doi: 10.3390/cells8101198.
Show Gene links
Show Anatomy links
Update on the Role of the Non-Canonical Wnt/Planar Cell Polarity Pathway in Neural Tube Defects.
Wang M
,
Marco P
,
Capra V
,
Kibar Z
.
???displayArticle.abstract???
Neural tube defects (NTDs), including spina bifida and anencephaly, represent the most severe and common malformations of the central nervous system affecting 0.7-3 per 1000 live births. They result from the failure of neural tube closure during the first few weeks of pregnancy. They have a complex etiology that implicate a large number of genetic and environmental factors that remain largely undetermined. Extensive studies in vertebrate models have strongly implicated the non-canonical Wnt/planar cell polarity (PCP) signaling pathway in the pathogenesis of NTDs. The defects in this pathway lead to a defective convergent extension that is a major morphogenetic process essential for neural tube elongation and subsequent closure. A large number of genetic studies in human NTDs have demonstrated an important role of PCP signaling in their etiology. However, the relative contribution of this pathway to this complex etiology awaits a better picture of the complete genetic architecture of these defects. The emergence of new genome technologies and bioinformatics pipelines, complemented with the powerful tool of animal models for variant interpretation as well as significant collaborative efforts, will help to dissect the complex genetics of NTDs. The ultimate goal is to develop better preventive and counseling strategies for families affected by these devastating conditions.
???displayArticle.pubmedLink??? 31590237
???displayArticle.pmcLink??? PMC6829399
???displayArticle.link??? Cells
Genes referenced: dvl2 fubp1 npb
???attribute.lit??? ???displayArticles.show???
Figure 1. Normal and abnormal neural tube formation. (A) Major steps of neural tube formation. The neural plate overlying the notochord elevates to form the neural folds around the midline, bends at the midline (mhp) and dorsolateral sites (dlhp) then fuses at the opposing tips of the neural folds and separates from the overlying epidermis. (B). Initiation sites of neural tube closure 1–3 in a mouse embryo. Defects in closure 1 and 2 lead to craniorachischisis and anencephaly respectively. Defects in closure at the caudal end of site 1 lead to open spina bifida. (C). Lateral and dorsal views of E18.5 embryos showing craniorachischisis (C′) and open spina bifida (C″, indicated by red arrows) as compared to wild type (C). cc, central canal; dlhp, dorsolateral hinge point; ec, ectoderm; ep, epidermis; fb, forebrain; hb, hindbrain; mb, midbrain; mhp, median hinge point; me, mesoderm; nc, notochord; ncp, notochordal plate; nec, neural crest; np, neural plate; npb, neural plate border; pe, presumptive epidermis; sc, spinal cord; so, somites. | |
Figure 2. The non-canonical Wnt/planar cell polarity signaling pathway (PCP). (A) A simplified diagram of the PCP signaling pathway showing its core components, its downstream effectors and two of its mediators Ptk7/Otk and Scribble1/Scrib. Nomenclature for core proteins is indicated in vertebrates and Drosophila (separated by/). Genetic interactions are indicated by double arrows. (B) An example of a PCP-regulated process in the wing blade of Drosophila. Asymmetric localization of PCP protein complexes at the proximal (Vang-Pk) and distal (Fz-Dsh) sides of adjacent cells mediates the distal positioning and orientation of a single trichome in each cell of the wing epithelium. (C) The process of convergent extension. Cells elongate mediolaterally, move and intercalate with neighboring cells resulting in convergence toward the midline and extension along the anteroposterior axis. During this process, PK and VANGL localize anteriorly whereas FZD and DVL localize posteriorly. (D) A simplified diagram showing a widened neural plate because of a defective convergent extension (CE) of midline neuroepithelial cells. The neural folds will be far apart and will fail to fuse leading to a neural tube defect. |
References [+] :
Abdul-Aziz,
EphrinA-EphA receptor interactions in mouse spinal neurulation: implications for neural fold fusion.
2009, Pubmed
Abdul-Aziz, EphrinA-EphA receptor interactions in mouse spinal neurulation: implications for neural fold fusion. 2009, Pubmed
Allache, Role of the planar cell polarity gene CELSR1 in neural tube defects and caudal agenesis. 2012, Pubmed
Allache, Novel mutations in Lrp6 orthologs in mouse and human neural tube defects affect a highly dosage-sensitive Wnt non-canonical planar cell polarity pathway. 2014, Pubmed
Allache, Genetic studies of ANKRD6 as a molecular switch between Wnt signaling pathways in human neural tube defects. 2015, Pubmed
Anastas, WNT signalling pathways as therapeutic targets in cancer. 2013, Pubmed
Andersson, Genetic interaction between Lrp6 and Wnt5a during mouse development. 2010, Pubmed
Assémat, Polarity complex proteins. 2008, Pubmed
Avagliano, Overview on neural tube defects: From development to physical characteristics. 2019, Pubmed
Barrow, Wnt/PCP signaling: a veritable polar star in establishing patterns of polarity in embryonic tissues. 2006, Pubmed
Bartsch, Novel VANGL1 Gene Mutations in 144 Slovakian, Romanian and German Patients with Neural Tube Defects. 2012, Pubmed
Bassuk, Genetic basis of neural tube defects. 2009, Pubmed
Bin-Nun, PTK7 modulates Wnt signaling activity via LRP6. 2014, Pubmed , Xenbase
Blencowe, Estimates of global and regional prevalence of neural tube defects for 2015: a systematic analysis. 2018, Pubmed
Blom, Neural tube defects and folate: case far from closed. 2006, Pubmed
Bosoi, Identification and characterization of novel rare mutations in the planar cell polarity gene PRICKLE1 in human neural tube defects. 2011, Pubmed
Boyle, An Expanded View of Complex Traits: From Polygenic to Omnigenic. 2017, Pubmed
Bryja, The extracellular domain of Lrp5/6 inhibits noncanonical Wnt signaling in vivo. 2009, Pubmed , Xenbase
Butler, Planar cell polarity in development and disease. 2017, Pubmed
Cai, Association between VANGL1 gene polymorphisms and neural tube defects. 2014, Pubmed
Camerer, Local protease signaling contributes to neural tube closure in the mouse embryo. 2010, Pubmed
Carter, Crooked tail (Cd) model of human folate-responsive neural tube defects is mutated in Wnt coreceptor lipoprotein receptor-related protein 6. 2005, Pubmed
Catala, Genetic control of caudal development. 2002, Pubmed
Chen, Threshold for neural tube defect risk by accumulated singleton loss-of-function variants. 2018, Pubmed
Chen, Genetic analysis of Wnt/PCP genes in neural tube defects. 2018, Pubmed
Copp, Neural tube defects: recent advances, unsolved questions, and controversies. 2013, Pubmed
Curtin, Mutation of Celsr1 disrupts planar polarity of inner ear hair cells and causes severe neural tube defects in the mouse. 2003, Pubmed
De Marco, Genetic analysis of disheveled 2 and disheveled 3 in human neural tube defects. 2013, Pubmed
De Marco, FZD6 is a novel gene for human neural tube defects. 2012, Pubmed
Detrait, Human neural tube defects: developmental biology, epidemiology, and genetics. 2005, Pubmed
Doudney, Analysis of the planar cell polarity gene Vangl2 and its co-expressed paralogue Vangl1 in neural tube defect patients. 2005, Pubmed
Etheridge, Murine dishevelled 3 functions in redundant pathways with dishevelled 1 and 2 in normal cardiac outflow tract, cochlea, and neural tube development. 2008, Pubmed
Gibson, Rare and common variants: twenty arguments. 2012, Pubmed
Greene, Inositol, neural tube closure and the prevention of neural tube defects. 2017, Pubmed
Greene, Inositol for the prevention of neural tube defects: a pilot randomised controlled trial. 2016, Pubmed
Haigo, Shroom induces apical constriction and is required for hingepoint formation during neural tube closure. 2003, Pubmed , Xenbase
Halaoui, Rewiring cell polarity signaling in cancer. 2015, Pubmed
Harris, An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure. 2010, Pubmed
Hayes, ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease. 2014, Pubmed
Hayes, Ptk7 promotes non-canonical Wnt/PCP-mediated morphogenesis and inhibits Wnt/β-catenin-dependent cell fate decisions during vertebrate development. 2013, Pubmed , Xenbase
Henderson, Planar cell polarity in organ formation. 2018, Pubmed
Huebner, Coming to Consensus: A Unifying Model Emerges for Convergent Extension. 2018, Pubmed
Humphries, From instruction to output: Wnt/PCP signaling in development and cancer. 2018, Pubmed
Juriloff, A consideration of the evidence that genetic defects in planar cell polarity contribute to the etiology of human neural tube defects. 2012, Pubmed
Kharfallah, Scribble1 plays an important role in the pathogenesis of neural tube defects through its mediating effect of Par-3 and Vangl1/2 localization. 2017, Pubmed
Kibar, Novel mutations in VANGL1 in neural tube defects. 2009, Pubmed
Kibar, Contribution of VANGL2 mutations to isolated neural tube defects. 2011, Pubmed
Kibar, Ltap, a mammalian homolog of Drosophila Strabismus/Van Gogh, is altered in the mouse neural tube mutant Loop-tail. 2001, Pubmed
Kibar, Mutations in VANGL1 associated with neural-tube defects. 2007, Pubmed
Lei, VANGL2 mutations in human cranial neural-tube defects. 2010, Pubmed
Lei, Rare LRP6 variants identified in spina bifida patients. 2015, Pubmed
Lei, Identification of novel CELSR1 mutations in spina bifida. 2014, Pubmed
Lei, Mutations in planar cell polarity gene SCRIB are associated with spina bifida. 2013, Pubmed
Lei, Variants identified in PTK7 associated with neural tube defects. 2019, Pubmed
Lemay, Loss-of-function de novo mutations play an important role in severe human neural tube defects. 2015, Pubmed
Lu, PTK7/CCK-4 is a novel regulator of planar cell polarity in vertebrates. 2004, Pubmed , Xenbase
Lynch, Non-multifactorial neural tube defects. 2005, Pubmed
Macheda, The Wnt receptor Ryk plays a role in mammalian planar cell polarity signaling. 2012, Pubmed
Martin, Morphogenesis: shroom in to close the neural tube. 2004, Pubmed
Massarwa, Morphogenetic movements in the neural plate and neural tube: mouse. 2014, Pubmed
Maung, Planar cell polarity in Drosophila. 2011, Pubmed
McGreevy, Shroom3 functions downstream of planar cell polarity to regulate myosin II distribution and cellular organization during neural tube closure. 2015, Pubmed
McNeill, Planar cell polarity: keeping hairs straight is not so simple. 2010, Pubmed
Merello, Expanding the mutational spectrum associated to neural tube defects: literature revision and description of novel VANGL1 mutations. 2015, Pubmed
Milgrom-Hoffman, Regulation of cellular and PCP signalling by the Scribble polarity module. 2018, Pubmed
Minami, Ror-family receptor tyrosine kinases in noncanonical Wnt signaling: their implications in developmental morphogenesis and human diseases. 2010, Pubmed
Montcouquiol, Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. 2003, Pubmed
Mosley, Neural tube defects and maternal folate intake among pregnancies conceived after folic acid fortification in the United States. 2009, Pubmed
Murdoch, Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse. 2003, Pubmed
Murdoch, Genetic interactions between planar cell polarity genes cause diverse neural tube defects in mice. 2014, Pubmed
Murdoch, Severe neural tube defects in the loop-tail mouse result from mutation of Lpp1, a novel gene involved in floor plate specification. 2001, Pubmed
NULL, Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. 1991, Pubmed
Niehrs, The complex world of WNT receptor signalling. 2012, Pubmed
Nikolopoulou, Neural tube closure: cellular, molecular and biomechanical mechanisms. 2017, Pubmed
Nusse, Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. 1982, Pubmed
Nusse, Three decades of Wnts: a personal perspective on how a scientific field developed. 2012, Pubmed , Xenbase
Nusse, Wnt/β-Catenin Signaling, Disease, and Emerging Therapeutic Modalities. 2017, Pubmed
Pai, Epithelial fusion during neural tube morphogenesis. 2012, Pubmed
Peradziryi, PTK7/Otk interacts with Wnts and inhibits canonical Wnt signalling. 2011, Pubmed , Xenbase
Pinson, An LDL-receptor-related protein mediates Wnt signalling in mice. 2000, Pubmed
Puppo, Protein tyrosine kinase 7 has a conserved role in Wnt/β-catenin canonical signalling. 2011, Pubmed , Xenbase
Pyrgaki, Grainyhead-like 2 regulates neural tube closure and adhesion molecule expression during neural fold fusion. 2011, Pubmed
Qiao, Genetic analysis of rare coding mutations of CELSR1-3 in congenital heart and neural tube defects in Chinese people. 2016, Pubmed
Reynolds, VANGL1 rare variants associated with neural tube defects affect convergent extension in zebrafish. 2010, Pubmed
Robinson, Mutations in the planar cell polarity genes CELSR1 and SCRIB are associated with the severe neural tube defect craniorachischisis. 2012, Pubmed
Rolo, Regulation of cell protrusions by small GTPases during fusion of the neural folds. 2016, Pubmed
Rossi, Imaging in spine and spinal cord malformations. 2004, Pubmed
Roszko, Regulation of convergence and extension movements during vertebrate gastrulation by the Wnt/PCP pathway. 2009, Pubmed
Sawyer, Apical constriction: a cell shape change that can drive morphogenesis. 2010, Pubmed , Xenbase
Sebbagh, Insight into planar cell polarity. 2014, Pubmed
Shindo, Models of convergent extension during morphogenesis. 2018, Pubmed , Xenbase
Tada, Convergent extension: using collective cell migration and cell intercalation to shape embryos. 2012, Pubmed , Xenbase
Tahinci, Lrp6 is required for convergent extension during Xenopus gastrulation. 2007, Pubmed , Xenbase
Van Allen, Evidence for multi-site closure of the neural tube in humans. 1993, Pubmed
Van Allen, Multisite neural tube closure in humans. 1996, Pubmed
VanderVorst, Wnt/PCP Signaling Contribution to Carcinoma Collective Cell Migration and Metastasis. 2019, Pubmed
Veltman, De novo mutations in human genetic disease. 2012, Pubmed
Vladar, Planar cell polarity signaling: the developing cell's compass. 2009, Pubmed
Wallingford, Strange as it may seem: the many links between Wnt signaling, planar cell polarity, and cilia. 2011, Pubmed , Xenbase
Wallingford, Neural tube closure and neural tube defects: studies in animal models reveal known knowns and known unknowns. 2005, Pubmed
Wang, Digenic variants of planar cell polarity genes in human neural tube defect patients. 2018, Pubmed
Wang, The role of Frizzled3 and Frizzled6 in neural tube closure and in the planar polarity of inner-ear sensory hair cells. 2006, Pubmed
Wang, De novo Mutations From Whole Exome Sequencing in Neurodevelopmental and Psychiatric Disorders: From Discovery to Application. 2019, Pubmed
Wang, Tissue/planar cell polarity in vertebrates: new insights and new questions. 2007, Pubmed
Wang, Role of the planar cell polarity gene Protein tyrosine kinase 7 in neural tube defects in humans. 2015, Pubmed
Weidinger, When Wnts antagonize Wnts. 2003, Pubmed
Yang, Wnt-Frizzled/planar cell polarity signaling: cellular orientation by facing the wind (Wnt). 2015, Pubmed
Ybot-Gonzalez, Sonic hedgehog and the molecular regulation of mouse neural tube closure. 2002, Pubmed , Xenbase
Ybot-Gonzalez, Convergent extension, planar-cell-polarity signalling and initiation of mouse neural tube closure. 2007, Pubmed
Ybot-Gonzalez, Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling. 2007, Pubmed
de Bakker, Single-site neural tube closure in human embryos revisited. 2017, Pubmed
Žigman, Zebrafish neural tube morphogenesis requires Scribble-dependent oriented cell divisions. 2011, Pubmed