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Vangl2–environment interaction causes severe neural tube defects, without abnormal neuroepithelial convergent extension
- Source :
- Disease Models & Mechanisms, article-version (VoR) Version of Record
- Publication Year :
- 2022
- Publisher :
- The Company of Biologists Ltd, 2022.
-
Abstract
- Planar cell polarity (PCP) signalling is vital for initiation of mouse neurulation, with diminished convergent extension (CE) cell movements leading to craniorachischisis, a severe neural tube defect (NTD). Some humans with NTDs also have PCP gene mutations but these are heterozygous, not homozygous as in mice. Other genetic or environmental factors may interact with partial loss of PCP function in human NTDs. We found that reduced sulfation of glycosaminoglycans interacts with heterozygosity for the Lp allele of Vangl2 (a core PCP gene), to cause craniorachischisis in cultured mouse embryos, with rescue by exogenous sulphate. We hypothesized that this glycosaminoglycan–PCP interaction may regulate CE, but, surprisingly, DiO labelling of the embryonic node demonstrates no abnormality of midline axial extension in sulfation-depleted Lp/+ embryos. Positive-control Lp/Lp embryos show severe CE defects. Abnormalities were detected in the size and shape of somites that flank the closing neural tube in sulfation-depleted Lp/+ embryos. We conclude that failure of closure initiation can arise by a mechanism other than faulty neuroepithelial CE, with possible involvement of matrix-mediated somite expansion, adjacent to the closing neural tube.<br />Summary: A gene–environment interaction involving the Vangl2 gene and sulfated glycosaminoglycans prevents mouse neural tube closure. Convergent extension shaping of the embryo is unaffected, implicating other mechanism(s) in this process.
- Subjects :
- Neural Tube
Mouse
Neuroscience (miscellaneous)
Medicine (miscellaneous)
Nerve Tissue Proteins
Gene mutation
Biology
General Biochemistry, Genetics and Molecular Biology
Mice
Immunology and Microbiology (miscellaneous)
medicine
Craniorachischisis
Developmental Disorders
Animals
Embryo culture
Neural Tube Defects
Neurulation
Glycosaminoglycans
Neural tube defect
Convergent extension
Neural tube
Cell Polarity
medicine.disease
Planar cell polarity
Cell biology
Neuroepithelial cell
Organoids
Somite
medicine.anatomical_structure
Proteoglycans
Gene-Environment Interaction
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 17548411 and 17548403
- Volume :
- 15
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Disease Models & Mechanisms
- Accession number :
- edsair.doi.dedup.....b30b748e9803c07bc67cf9093c00cc46