Background:VANGL2 plays a variety of roles in various cellular processes, including tissue morphogenesis, asymmetric cell division, and nervous system development. There is currently a lack of systematic organization in the development and disease of the nervous system. Purpose: To explore the role of VANGL2 in the development of the nervous system and related diseases. Methods: Literature review and analysis of the role of VANGL2 in the development and disease of the nervous system. Results:VANGL2 defects lead to the development of the nervous system through the misconfiguration of various cells, which affects the development of the cochlea, the conduction of neural signals, and the development of nervous system-related diseases such as Alzheimer’s disease, GBM, Bohling-Opitz syndrome, and hydrocephalus. Conclusions:The VANGL2 gene is essential for nervous system development and its deficiency is linked to severe congenital conditions and various disorders, highlighting the need for more research on treatments for related gene defects.
References
[1]
Mentink, R.A., Rella, L., Radaszkiewicz, T.W., Gybel, T., Betist, M.C., Bryja, V., et al. (2018) The Planar Cell Polarity Protein VANG-1/Vangl Negatively Regulates Wnt/β-Catenin Signaling through a Dvl Dependent Mechanism. PLOS Genetics, 14, e1007840. https://doi.org/10.1371/journal.pgen.1007840
[2]
Lawrence, P.A. and Casal, J. (2013) The Mechanisms of Planar Cell Polarity, Growth and the Hippo Pathway: Some Known Unknowns. Developmental Biology, 377, 1-8. https://doi.org/10.1016/j.ydbio.2013.01.030
[3]
Yang, Y. and Mlodzik, M. (2015) Wnt-Frizzled/Planar Cell Polarity Signaling: Cellular Orientation by Facing the Wind (Wnt). Annual Review of Cell and Developmental Biology, 31, 623-646. https://doi.org/10.1146/annurev-cellbio-100814-125315
[4]
Yasumura, M., Hagiwara, A., Hida, Y. and Ohtsuka, T. (2021) Planar Cell Polarity Protein VANGL2 and Its Interacting Protein Ap2m1 Regulate Dendritic Branching in Cortical Neurons. Genes to Cells, 26, 987-998. https://doi.org/10.1111/gtc.12899
[5]
Strutt, H., Warrington, S.J. and Strutt, D. (2011) Dynamics of Core Planar Polarity Protein Turnover and Stable Assembly into Discrete Membrane Subdomains. Developmental Cell, 20, 511-525. https://doi.org/10.1016/j.devcel.2011.03.018
[6]
Butler, M.T. and Wallingford, J.B. (2017) Planar Cell Polarity in Development and Disease. Nature Reviews Molecular Cell Biology, 18, 375-388. https://doi.org/10.1038/nrm.2017.11
[7]
Galea, G.L., Nychyk, O., Mole, M.A., Moulding, D., Savery, D., Nikolopoulou, E., et al. (2018) VANGL2 Disruption Alters the Biomechanics of Late Spinal Neurulation Leading to Spina Bifida in Mouse Embryos. Disease Models & Mechanisms, 11, Article dmm032219. https://doi.org/10.1242/dmm.032219
[8]
Jarjour, A.A., Velichkova, A.N., Boyd, A., Lord, K.M., Torsney, C., Henderson, D.J., et al. (2020) The Formation of Paranodal Spirals at the Ends of CNS Myelin Sheaths Requires the Planar Polarity Protein VANGL2. Glia, 68, 1840-1858. https://doi.org/10.1002/glia.23809
[9]
Zhang, K., Yao, E., Wang, S.A., Chuang, E., Wong, J., Minichiello, L., et al. (2022) A Functional Circuit Formed by the Autonomic Nerves and Myofibroblasts Controls Mammalian Alveolar Formation for Gas Exchange. Developmental Cell, 57, 1566-1581. https://doi.org/10.1016/j.devcel.2022.05.021
[10]
Jussila, M., Boswell, C.W., Griffiths, N.W., Pumputis, P.G. and Ciruna, B. (2022) Live Imaging and Conditional Disruption of Native PCP Activity Using Endogenously Tagged Zebrafish SfGFP-VANGL2. Nature Communications, 13, Article No. 5598. https://doi.org/10.1038/s41467-022-33322-9
[11]
Copp, A.J., Stanier, P. and Greene, N.D.E. (2013) Neural Tube Defects: Recent Advances, Unsolved Questions, and Controversies. The Lancet Neurology, 12, 799-810. https://doi.org/10.1016/s1474-4422(13)70110-8
[12]
Blom, H.J., Shaw, G.M., den Heijer, M. and Finnell, R.H. (2006) Neural Tube Defects and Folate: Case Far from Closed. Nature Reviews Neuroscience, 7, 724-731. https://doi.org/10.1038/nrn1986
[13]
Butler, M.T. and Wallingford, J.B. (2015) Control of Vertebrate Core PCP Protein Localization and Dynamics by Prickle2. Development, 142, 3429-3429. https://doi.org/10.1242/dev.121384
[14]
Wallingford, J.B. (2005) Neural Tube Closure and Neural Tube Defects: Studies in Animal Models Reveal Known Knowns and Known Unknowns. American Journal of Medical Genetics Part C: Seminars in Medical Genetics, 135, 59-68. https://doi.org/10.1002/ajmg.c.30054
[15]
Tada, M. and Heisenberg, C.-P. (2012) Convergent Extension: Using Collective Cell Migration and Cell Intercalation to Shape Embryos. Development, 139, 3897-3904. https://doi.org/10.1242/dev.073007
[16]
Shindo, A. (2017) Models of Convergent Extension during Morphogenesis. WIREs Developmental Biology, 7, e293. https://doi.org/10.1002/wdev.293
[17]
López-Escobar, B., Caro-Vega, J.M., Vijayraghavan, D.S., Plageman, T.F., Sanchez-Alcazar, J.A., Moreno, R.C., et al. (2018) The Non-Canonical Wnt-PCP Pathway Shapes the Caudal Neural Plate. Development, 145, Article dev157487. https://doi.org/10.1242/dev.157487
[18]
Shah, P.K., Tanner, M.R., Kovacevic, I., Rankin, A., Marshall, T.E., Noblett, N., et al. (2017) PCP and SAX-3/Robo Pathways Cooperate to Regulate Convergent Extension-Based Nerve Cord Assembly in C. Elegans. Developmental Cell, 41, 195-203. https://doi.org/10.1016/j.devcel.2017.03.024
[19]
Prager, A., Hagenlocher, C., Ott, T., Schambony, A. and Feistel, K. (2017) Hmmr Mediates Anterior Neural Tube Closure and Morphogenesis in the Frog Xenopus. Developmental Biology, 430, 188-201. https://doi.org/10.1016/j.ydbio.2017.07.020
[20]
Nagaoka, T., Katsuno, T., Fujimura, K., Tsuchida, K. and Kishi, M. (2023) Functional Interaction between VANGL2 and N-Cadherin Regulates Planar Cell Polarization of the Developing Neural Tube and Cochlear Sensory Epithelium. Scientific Reports, 13, Article No. 3905. https://doi.org/10.1038/s41598-023-30213-x
[21]
Dos-Santos Carvalho, S., Moreau, M.M., Hien, Y.E., Garcia, M., Aubailly, N., Henderson, D.J., et al. (2020) VANGL2 Acts at the Interface between Actin and N-Cadherin to Modulate Mammalian Neuronal Outgrowth. eLife, 9, e51822. https://doi.org/10.7554/elife.51822
[22]
Seo, H.-S., Habas, R., Chang, C. and Wang, J. (2017) Bimodal Regulation of Dishevelled Function by VANGL2 during Morphogenesis. Human Molecular Genetics, 26, 2053-2061. https://doi.org/10.1093/hmg/ddx095
[23]
Ohata, S., Uga, H., Okamoto, H. and Katada, T. (2018) Small Gtpase R-Ras Participates in Neural Tube Formation in Zebrafish Embryonic Spinal Cord. Biochemical and Biophysical Research Communications, 501, 786-790. https://doi.org/10.1016/j.bbrc.2018.05.074
[24]
Guo, S.S., Au, T.Y.K., Wynn, S., Aszodi, A., Chan, D., Fässler, R., et al. (2020) β1 Integrin Regulates Convergent Extension in Mouse Notogenesis, Ensures Notochord Integrity and the Morphogenesis of Vertebrae and Intervertebral Discs. Development, 147, Article dev192724. https://doi.org/10.1242/dev.192724
[25]
De Castro, S.C.P., Gustavsson, P., Marshall, A.R., Gordon, W.M., Galea, G., Nikolopoulou, E., et al. (2018) Overexpression of Grainyhead-Like 3 Causes Spina Bifida and Interacts Genetically with Mutant Alleles of Grhl2 and VANGL2 in Mice. Human Molecular Genetics, 27, 4218-4230. https://doi.org/10.1093/hmg/ddy313
[26]
Bellchambers, H.M. and Ware, S.M. (2021) Loss of Zic3 Impairs Planar Cell Polarity Leading to Abnormal Left-Right Signaling, Heart Defects and Neural Tube Defects. Human Molecular Genetics, 30, 2402-2415. https://doi.org/10.1093/hmg/ddab195
[27]
Lei, Y., Kim, S.E., Chen, Z., Cao, X., Zhu, H., Yang, W., et al. (2019) Variants Identified in PTK7 Associated with Neural Tube Defects. Molecular Genetics & Genomic Medicine, 7, e00584. https://doi.org/10.1002/mgg3.584
[28]
Tian, T., Lei, Y., Chen, Y., Guo, Y., Jin, L., Finnell, R.H., et al. (2020) Rare Copy Number Variations of Planar Cell Polarity Genes Are Associated with Human Neural Tube Defects. Neurogenetics, 21, 217-225. https://doi.org/10.1007/s10048-020-00613-6
[29]
Wang, L., Xiao, Y., Tian, T., Jin, L., Lei, Y., Finnell, R.H., et al. (2018) Digenic Variants of Planar Cell Polarity Genes in Human Neural Tube Defect Patients. Molecular Genetics and Metabolism, 124, 94-100. https://doi.org/10.1016/j.ymgme.2018.03.005
[30]
Ulmer, B., Tingler, M., Kurz, S., Maerker, M., Andre, P., Mönch, D., et al. (2017) A Novel Role of the Organizer Gene Goosecoid as an Inhibitor of Wnt/PCP-Mediated Convergent Extension in Xenopus and Mouse. Scientific Reports, 7, Article No. 43010. https://doi.org/10.1038/srep43010
[31]
Boëx, M., Messéant, J., Cottin, S., Halliez, M., Bauché, S., et al. (2020) Muscle Van Gogh-Like 2 Shapes the Neuromuscular Synapse by Regulating MuSK Signaling Activity.
[32]
Gurung, S., Asante, E., Hummel, D., Williams, A., Feldman-Schultz, O., Halloran, M.C., et al. (2018) Distinct Roles for the Cell Adhesion Molecule Contactin2 in the Development and Function of Neural Circuits in Zebrafish. Mechanisms of Development, 152, 1-12. https://doi.org/10.1016/j.mod.2018.05.005
[33]
Messéant, J., Ezan, J., Delers, P., Glebov, K., Marchiol, C., Lager, F., et al. (2017) Wnt Proteins Contribute to Neuromuscular Junction Formation through Distinct Signaling Pathways. Development, 144, 1712-1724. https://doi.org/10.1242/dev.146167
[34]
Duan, X., Gao, Y. and Liu, Y. (2017) Ryk Regulates Wnt5a Repulsion of Mouse Corticospinal Tract through Modulating Planar Cell Polarity Signaling. Cell Discovery, 3, Article No. 17015. https://doi.org/10.1038/celldisc.2017.15
[35]
Ghimire, S.R. and Deans, M.R. (2019) Frizzled3and Frizzled6Cooperate with VANGL2to Direct Cochlear Innervation by Type II Spiral Ganglion Neurons. The Journal of Neuroscience, 39, 8013-8023. https://doi.org/10.1523/jneurosci.1740-19.2019
[36]
Ghimire, S.R., Ratzan, E.M. and Deans, M.R. (2018) A Non-Autonomous Function of the Core PCP Protein VANGL2 Directs Peripheral Axon Turning in the Developing Cochlea. Development, 145, Article dev159012. https://doi.org/10.1242/dev.159012
[37]
Najarro, E.H., Huang, J., Jacobo, A., Quiruz, L.A., Grillet, N. and Cheng, A.G. (2020) Dual Regulation of Planar Polarization by Secreted Wnts and VANGL2 in the Developing Mouse Cochlea. Development, 147, Article dev191981.
[38]
Elliott, C., Rojo, A.I., Ribe, E., Broadstock, M., Xia, W., Morin, P., et al. (2018) A Role for APP in Wnt Signalling Links Synapse Loss with β-Amyloid Production. Translational Psychiatry, 8, Article No. 179. https://doi.org/10.1038/s41398-018-0231-6
[39]
Wald, J.H., Hatakeyama, J., Printsev, I., Cuevas, A., Fry, W.H.D., Saldana, M.J., et al. (2017) Suppression of Planar Cell Polarity Signaling and Migration in Glioblastoma by Nrdp1-Mediated Dvl Polyubiquitination. Oncogene, 36, 5158-5167. https://doi.org/10.1038/onc.2017.126
[40]
Duffy, D.J., Konietzny, A., Krstic, A., Mehta, J.P., Halasz, M. and Kolch, W. (2018) Identification of a MYCN and Wnt-Related VANGL2-ITLN1 Fusion Gene in Neuroblastoma. Gene Reports, 12, 187-200. https://doi.org/10.1016/j.genrep.2018.06.018
[41]
Lin, I., Wei, A., Awamleh, Z., Singh, M., Ning, A., Herrera, A., et al. (2023) Multiomics of Bohring-Opitz Syndrome Truncating ASXL1 Mutations Identify Canonical and Noncanonical Wnt Signaling Dysregulation. JCI Insight, 8, e167744. https://doi.org/10.1172/jci.insight.167744
[42]
Treat, A.C., Wheeler, D.S., Stolz, D.B., Tsang, M., Friedman, P.A. and Romero, G. (2016) The PDZ Protein Na+/H+ Exchanger Regulatory Factor-1 (NHERF1) Regulates Planar Cell Polarity and Motile Cilia Organization. PLOS ONE, 11, e0153144. https://doi.org/10.1371/journal.pone.0153144
