Show simple item record

dc.contributor.authorGalea, Gabriel L.
dc.contributor.authorNychyk, Oleksandr
dc.contributor.authorMole, Matteo A.
dc.contributor.authorMoulding, Dale
dc.contributor.authorSavery, Dawn
dc.contributor.authorNikolopoulou, Evanthia
dc.contributor.authorHenderson, Deborah J.
dc.contributor.authorGreene, Nicholas D. E.
dc.contributor.authorCopp, Andrew J.
dc.date.accessioned2020-08-20T16:09:18Z
dc.date.available2020-08-20T16:09:18Z
dc.date.issued2018-03-12
dc.identifier.citationGalea, G. L., Nychyk, O., Mole, M. A., Moulding, D., Savery, D., Nikopolou, E., Henderson, D., Greene, N. D., Copp, A. Vangl2 disruption alters the biomechanics of late spinal neurulation leading to spina bifida in mouse embryos. Disease Models & Mechanisms, 2018, 11: dmm032219. doi: https://doi.org/10.1242/dmm.032219en_US
dc.identifier.issn1754-8403
dc.identifier.issn1754-8411
dc.identifier.urihttp://hdl.handle.net/11019/2309
dc.descriptionpeer-revieweden_US
dc.description.abstractHuman mutations in the planar cell polarity component VANGL2 are associated with the neural tube defect spina bifida. Homozygous Vangl2 mutation in mice prevents initiation of neural tube closure, precluding analysis of its subsequent roles in neurulation. Spinal neurulation involves rostral-to-caudal ‘zippering’ until completion of closure is imminent, when a caudal-to-rostral closure point, ‘Closure 5’, arises at the caudal-most extremity of the posterior neuropore (PNP). Here, we used Grhl3Cre to delete Vangl2 in the surface ectoderm (SE) throughout neurulation and in an increasing proportion of PNP neuroepithelial cells at late neurulation stages. This deletion impaired PNP closure after the ∼25-somite stage and resulted in caudal spina bifida in 67% of Grhl3Cre/+Vangl2Fl/Fl embryos. In the dorsal SE, Vangl2 deletion diminished rostrocaudal cell body orientation, but not directional polarisation of cell divisions. In the PNP, Vangl2 disruption diminished mediolateral polarisation of apical neuroepithelial F-actin profiles and resulted in eversion of the caudal PNP. This eversion prevented elevation of the caudal PNP neural folds, which in control embryos is associated with formation of Closure 5 around the 25-somite stage. Closure 5 formation in control embryos is associated with a reduction in mechanical stress withstood at the main zippering point, as inferred from the magnitude of neural fold separation following zippering point laser ablation. This stress accommodation did not happen in Vangl2-disrupted embryos. Thus, disruption of Vangl2-dependent planar-polarised processes in the PNP neuroepithelium and SE preclude zippering point biomechanical accommodation associated with Closure 5 formation at the completion of PNP closure.en_US
dc.language.isoen_USen_US
dc.publisherThe Company of Biologistsen_US
dc.relation.ispartofseriesDisease Models and Mechanisms;11
dc.rightsAttribution-ShareAlike 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-sa/3.0/us/*
dc.subjectNeural tubeen_US
dc.subjectVangl2en_US
dc.subjectBiomechanicsen_US
dc.subjectF-actinen_US
dc.subjectMouseen_US
dc.subjectembryoen_US
dc.titleVangl2 disruption alters the biomechanics of late spinal neurulation leading to spina bifida in mouse embryosen_US
dc.typeArticleen_US
dc.identifier.doihttps://doi.org/10.1242/dmm.032219
dc.source.volume11
dc.source.issue3
dc.source.beginpagedmm032219
refterms.dateFOA2020-08-20T16:09:18Z


Files in this item

Thumbnail
Name:
dmm032219.full.pdf
Size:
4.518Mb
Format:
PDF
Description:
main article

This item appears in the following Collection(s)

Show simple item record

Attribution-ShareAlike 3.0 United States
Except where otherwise noted, this item's license is described as Attribution-ShareAlike 3.0 United States