Role of the planar cell polarity geneProtein tyrosine kinase 7in neural tube defects in humans

2015 ◽  
Vol 103 (12) ◽  
pp. 1021-1027 ◽  
Author(s):  
Mingqin Wang ◽  
Patrizia De Marco ◽  
Elisa Merello ◽  
Pierre Drapeau ◽  
Valeria Capra ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity

scholarly journals Update on the Role of the Non-Canonical Wnt/Planar Cell Polarity Pathway in Neural Tube Defects

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1198 ◽  
Author(s):  
Wang ◽  
Marco ◽  
Capra ◽  
Kibar
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Neural Tube Closure ◽  
Convergent Extension ◽  
Complex Genetics ◽  
Pcp Signaling ◽  
Canonical Wnt

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.

Role of the planar cell polarity gene CELSR1 in neural tube defects and caudal agenesis

2012 ◽  
Vol 94 (3) ◽  
pp. 176-181 ◽  
Author(s):  
Redouane Allache ◽  
Patrizia De Marco ◽  
Elisa Merello ◽  
Valeria Capra ◽  
Zoha Kibar
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Polarity Gene

scholarly journals Mutations in the planar cell polarity gene, Fuzzy, are associated with neural tube defects in humans

2015 ◽  
Author(s):  
J. H. Seo ◽  
Y. Zilber ◽  
S. Babayeva ◽  
J. Liu ◽  
P. Kyriakopoulos ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Polarity Gene

scholarly journals Neuropathological hallmarks of fetal hydrocephalus linked to CCDC88C pathogenic variants

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Florent Marguet ◽  
Myriam Vezain ◽  
Pascale Marcorelles ◽  
Séverine Audebert-Bellanger ◽  
Kévin Cassinari ◽  
...  
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Planar Cell Polarity ◽  
Wnt Signaling Pathway ◽  
Brain Lesions ◽  
Congenital Hydrocephalus ◽  
Compound Heterozygous ◽  
Pathogenic Variants ◽  
Defects Classification

AbstractThe prevalence of congenital hydrocephalus has been estimated at 1.1 per 1000 infants when including cases diagnosed before 1 year of age after exclusion of neural tube defects. Classification criteria are based either on CSF dynamics, pathophysiological mechanisms or associated lesions. Whereas inherited syndromic hydrocephalus has been associated with more than 100 disease-causing genes, only four genes are currently known to be linked to congenital hydrocephalus either isolated or as a major clinical feature: L1CAM, AP1S2, MPDZ and CCDC88C. In the past 10 years, pathogenic variants in CCDC88C have been documented but the neuropathology remains virtually unknown. We report the neuropathology of two foetuses from one family harbouring two novel compound heterozygous pathogenic variants in the CCDC88C gene: a maternally inherited indel in exon 22, c.3807_3809delinsACCT;p.(Gly1270Profs*53) and a paternally inherited deletion of exon 23, c.3967-?_c.4112-?;p.(Leu1323Argfs*10). Medical termination of pregnancy was performed at 18 and 23 weeks of gestation for severe bilateral ventriculomegaly. In both fetuses, brain lesions consisted of multifocal atresia-forking along the aqueduct of Sylvius and the central canal of the medulla, periventricular neuronal heterotopias and choroid plexus hydrops. The second fetus also presented lumbar myelomeningocele, left diaphragmatic hernia and bilateral renal agenesis. CCDC88C encodes the protein DAPLE which contributes to ependymal cell planar polarity by inhibiting the non-canonical Wnt signaling pathway and interacts with MPDZ and PARD3. Interestingly, heterozygous variants in PARD3 result in neural tube defects by defective tight junction formation and polarization process of the neuroepithelium. Besides, during organ formation Wnt signalling is a prerequisite for planar cell polarity pathway activation, and mutations in planar cell polarity genes lead to heart, lung and kidney malformations. Hence, candidate variants in CCDC88C should be carefully considered whether brain lesions are isolated or associated with malformations suspected to result from disorders of planar cell polarity.

scholarly journals Mutations associated with human neural tube defects display disrupted planar cell polarity in Drosophila

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ashley C Humphries ◽  
Sonali Narang ◽  
Marek Mlodzik
Keyword(s):  
Cell Polarity ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Developmental Disorders ◽  
Planar Cell Polarity ◽  
Causative Factor ◽  
Limited Data ◽  
Post Translational Modification ◽  
Pcp Signaling

Planar cell polarity (PCP) and neural tube defects (NTDs) are linked, with a subset of NTD patients found to harbor mutations in PCP genes, but there is limited data on whether these mutations disrupt PCP signaling in vivo. The core PCP gene Van Gogh (Vang), Vangl1/2 in mammals, is the most specific for PCP. We thus addressed potential causality of NTD-associated Vangl1/2 mutations, from either mouse or human patients, in Drosophila allowing intricate analysis of the PCP pathway. Introducing the respective mammalian mutations into Drosophila Vang revealed defective phenotypic and functional behaviors, with changes to Vang localization, post-translational modification, and mechanistic function, such as its ability to interact with PCP effectors. Our findings provide mechanistic insight into how different mammalian mutations contribute to developmental disorders and strengthen the link between PCP and NTD. Importantly, analyses of the human mutations revealed that each is a causative factor for the associated NTD.

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