ArticleHuman molecular genetics2018
Overexpression of Grainyhead-like 3 causes spina bifida and interacts genetically with mutant alleles of Grhl2 and Vangl2 in mice.
Article in Human molecular genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Meta-Analysis ofGenes · 2019Pooled it
- Article
- A non-coding insertional mutation of Grhl2 causes gene over-expression and multiple structural anomalies including cleft palate, spina bifida and encephalocele.Human molecular genetics · 2023Article
- The loop-tail mouse model displays open and closed caudal neural tube defects.Disease models & mechanisms · 2023Article
- Dysregulation of Grainyhead-like 3 expression causes widespread developmental defects.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- Grainyhead-like (Grhl) Target Genes in Development and Cancer.International journal of molecular sciences · 2022Review
- Vangl2-environment interaction causes severe neural tube defects, without abnormal neuroepithelial convergent extension.Disease models & mechanisms · 2022Article
- Hindbrain neuropore tissue geometry determines asymmetric cell-mediated closure dynamics in mouse embryos.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Epithelial dynamics shed light on the mechanisms underlying ear canal defects.Development (Cambridge, England) · 2020Article
- Non-neural surface ectodermal rosette formation and F-actin dynamics drive mammalian neural tube closure.Biochemical and biophysical research communications · 2020Article
- Functional Validation ofFrontiers in neuroscience · 2020Article
- Relationship between Single Nucleotide Polymorphisms ofInternational journal of molecular and cellular medicine · 2020Article
- Spinal neural tube closure depends on regulation of surface ectoderm identity and biomechanics by Grhl2.Nature communications · 2019Article
- Molecular Basis of Spina Bifida: Recent Advances and Future Prospectives.Journal of pediatric neurosciencesArticle
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 3 countries.
Funding
Abstract
The genetic basis of human neural tube defects (NTDs), such as anencephaly and spina bifida (SB), is complex and heterogeneous. Grainyhead-like genes represent candidates for involvement in NTDs based on the presence of SB and exencephaly in mice carrying loss-of-function alleles of Grhl2 or Grhl3. We found that reinstatement of Grhl3 expression, by bacterial artificial chromosome (BAC)-mediated transgenesis, prevents SB in Grhl3-null embryos, as in the Grhl3 hypomorphic curly tail strain. Notably, however, further increase in expression of Grhl3 causes highly penetrant SB. Grhl3 overexpression recapitulates the spinal NTD phenotype of loss-of-function embryos, although the underlying mechanism differs. However, it does not phenocopy other defects of Grhl3-null embryos such as abnormal axial curvature, cranial NTDs (exencephaly) or skin barrier defects, the latter being rescued by the Grhl3-transgene. Grhl2 and Grhl3 can form homodimers and heterodimers, suggesting a possible model in which defects arising from overexpression of Grhl3 result from sequestration of Grhl2 in heterodimers, mimicking Grhl2 loss of function. This hypothesis predicts that increased abundance of Grhl2 would have an ameliorating effect in Grhl3 overexpressing embryo. Instead, we observed a striking additive genetic interaction between Grhl2 and Grhl3 gain-of-function alleles. Severe SB arose in embryos in which both genes were expressed at moderately elevated levels that individually do not cause NTDs. Furthermore, moderate Grhl3 overexpression also interacted with the Vangl2Lp allele to cause SB, demonstrating genetic interaction with the planar cell polarity signalling pathway that is implicated in mouse and human NTDs.
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Registered trials
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