scholarly journals The role of primary cilia in the pathophysiology of neural tube defects

2012 ◽  
Vol 33 (4) ◽  
pp. E2 ◽  
Author(s):  
Timothy W. Vogel ◽  
Calvin S. Carter ◽  
Kingsley Abode-Iyamah ◽  
Qihong Zhang ◽  
Shenandoah Robinson
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Neural Development ◽  
Planar Cell Polarity ◽  
Primary Cilia ◽  
Integration Site ◽  
Genetics Research ◽  
Neural Tube Development ◽  
Insight Into

Neural tube defects (NTDs) are a set of disorders that occur from perturbation of normal neural development. They occur in open or closed forms anywhere along the craniospinal axis and often result from a complex interaction between environmental and genetic factors. One burgeoning area of genetics research is the effect of cilia signaling on the developing neural tube and how the disruption of primary cilia leads to the development of NTDs. Recent progress has implicated the hedgehog (Hh), wingless-type integration site family (Wnt), and planar cell polarity (PCP) pathways in primary cilia as involved in normal neural tube patterning. A set of disorders involving cilia function, known as ciliopathies, offers insight into abnormal neural development. In this article, the authors discuss the common ciliopathies, such as Meckel-Gruber and Joubert syndromes, that are associated with NTDs, and review cilia-related signaling cascades responsible for mammalian neural tube development. Understanding the contribution of cilia in the formation of NTDs may provide greater insight into this common set of pediatric neurological disorders.

Neural tube defects: role of lithium carbonate exposure in embryonic neural development in a murine model

2020 ◽  
Author(s):  
Shen Li ◽  
Danqing Luo ◽  
Huixuan Yue ◽  
Jianjun Lyu ◽  
Yanwei Yang ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Neural Development ◽  
Murine Model ◽  
Lithium Carbonate

scholarly journals The role of folate and one-carbon metabolism in brain development and hydrocephalus: a literature review

2017 ◽  
Vol 2 (1) ◽  
pp. 1
Author(s):  
Z. Shehata
Keyword(s):  
Cerebrospinal Fluid ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Carbon Metabolism ◽  
Treatment Options ◽  
Methyl Donors ◽  
Novel Treatment ◽  
One Carbon Metabolism ◽  
Insight Into

Folate metabolism has been known to influence the development of the nervous system, as found in the case of neural tube defects. Folates are a group of compounds involved in one-carbon metabolism, which is necessary for the formation of purine and thymidine nucleotides, as well as methionine and methyl donors. In addition to the well-documented role of folates within the pathogenesis of neural tube defects, current literature provides evidence that folate imbalances may play a significant role in the development and effects of hydrocephalus. This review considers the possibility that folate imbalances in hydrocephalic cerebrospinal fluid may be responsible for the neurological deficit seen in patients with this condition. Understanding the details of this potential imbalance may provide further insight into novel treatment options for hydrocephalus in the future.

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.

scholarly journals METTL3-Mediated m6A Modification is Involved in Neural Tube Defects via Modulating Wnt/β-Catenin Signaling Pathway

2021 ◽  
Author(s):  
Li Zhang ◽  
Rui Cao ◽  
Dandan Li ◽  
Yuqing Sun ◽  
Juan Zhang ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Theoretical Basis ◽  
Clinical Work ◽  
Folic Acid Deficiency ◽  
Acid Deficiency ◽  
Life Threatening ◽  
Neural Tube Development

Abstract Neural tube defects (NTDs) remain one of the most life-threatening birth defects affecting infants. Most patients with a NTDs eventually develop lifelong disability, which cause significant morbidity and mortality and seriously reduce the quality of life. Therefore, identifiable of novel pathogenic strategies for NTDs patients is urgently required. Increasing evidence indicates that METTL3-mediated m6A modification is present in many physiopathological processes of cell apoptosis and survival. Our results demonstrate that SAM play not only a compensatory role, SAM can also lead to m6A modification changes in neural tube development and regulation. This research provides a good theoretical basis for further research on folic acid deficiency leading to NTDs, reveals the important role of SAM in the development of NTDs, and provides new clue for clinical researchers and clinical work.

scholarly journals Nuclear factor I-C disrupts cellular homeostasis between autophagy and apoptosis via miR-200b-Ambra1 in neural tube defects

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Wanqi Huang ◽  
Tianchu Huang ◽  
Yusi Liu ◽  
Jialin Fu ◽  
Xiaowei Wei ◽  
...  
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Critical Role ◽  
Neural Tube Closure ◽  
Nuclear Factor ◽  
Cellular Homeostasis ◽  
Factor I ◽  
Nuclear Factor I ◽  
Insight Into

AbstractImpaired autophagy and excessive apoptosis disrupt cellular homeostasis and contribute to neural tube defects (NTDs), which are a group of fatal and disabling birth defects caused by the failure of neural tube closure during early embryonic development. However, the regulatory mechanisms underlying NTDs and outcomes remain elusive. Here, we report the role of the transcription factor nuclear factor I-C (NFIC) in maintaining cellular homeostasis in NTDs. We demonstrated that abnormally elevated levels of NFIC in a mouse model of NTDs can interact with the miR-200b promoter, leading to the activation of the transcription of miR-200b, which plays a critical role in NTD formation, as reported in our previous study. Furthermore, miR-200b represses autophagy and triggers apoptosis by directly targeting the autophagy-related gene Ambra1 (Autophagy/Beclin1 regulator 1). Notably, miR-200b inhibitors mitigate the unexpected effects of NFIC on autophagy and apoptosis. Collectively, these results indicate that the NFIC-miR-200b-Ambra1 axis, which integrates transcription- and epigenome-regulated miRNAs and an autophagy regulator, disrupts cellular homeostasis during the closure of the neural tube, and may provide new insight into NTD pathogenesis.

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 Independent Mutations in MouseVangl2That Cause Neural Tube Defects inLooptailMice Impair Interaction with Members of theDishevelledFamily

2004 ◽  
Vol 279 (50) ◽  
pp. 52703-52713 ◽  
Author(s):  
Elena Torban ◽  
Hui-Jun Wang ◽  
Normand Groulx ◽  
Philippe Gros
Keyword(s):  
Neural Tube ◽  
Neural Tube Defects ◽  
Neural Tube Defect ◽  
Planar Cell Polarity ◽  
Cell Types ◽  
Biochemical Properties ◽  
Model Organisms ◽  
Convergent Extension ◽  
Loss Of Function

Mammalian Vangl1 and Vangl2 are highly conserved membrane proteins that have evolved from a single ancestral proteinStrabismus/Van Goghfound inDrosophila. Mutations in theVangl2gene cause a neural tube defect (craniorachischisis) characteristic of thelooptail(Lp) mouse. Studies in model organisms indicate that Vangl proteins play a key developmental role in establishing planar cell polarity (PCP) and in regulating convergent extension (CE) movements during embryogenesis. The role of Vangl1 in these processes is virtually unknown, and the molecular function of Vangl1 and Vangl2 in PCP and CE is poorly understood. Using a yeast two-hybrid system, glutathioneS-transferase pull-down and co-immunoprecipitation assays, we show that both mouse Vangl1 and Vangl2 physically interact with the three members of the cytoplasmic Dishevelled (Dvl) protein family. This interaction is shown to require both the predicted cytoplasmic C-terminal half of Vangl1/2 and a portion of the Dvl protein containing PDZ and DIX domains. In addition, we show that the two knownVangl2loss-of-function mutations identified in two independentLpalleles associated with neural tube defects impair binding to Dvl1, Dvl2, and Dvl3. These findings suggest a molecular mechanism for the neural tube defect seen inLpmice. Our observations indicate that Vangl1 biochemical properties parallel those of Vangl2 and that Vangl1 might, therefore, participate in PCP and CE either in concert with Vangl2 or independently of Vangl2 in discrete cell types.

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 Ethionine-mediated reduction of S-adenosylmethionine is responsible for the neural tube defects in the developing mouse embryo-mediated m6A modification and is involved in neural tube defects via modulating Wnt/β-catenin signaling pathway

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Li Zhang ◽  
Rui Cao ◽  
Dandan Li ◽  
Yuqing Sun ◽  
Juan Zhang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Epigenetic Mechanism ◽  
Proliferation And Apoptosis ◽  
Life Threatening ◽  
Neural Tube Development

AbstractNeural tube defects (NTDs) remain one of the most life-threatening birth defects affecting infants. Most patients with NTDs eventually develop lifelong disability, which cause significant morbidity and mortality and seriously reduce the quality of life. Our previous study has found that ethionine inhibits cell viability by disrupting the balance between proliferation and apoptosis, and preventing neural stem cells from differentiating into neurons and astrocytes. However, how ethionine participates in the pathogenesis of neural tube development through N6-methyladenosine (m6A) modification remains unknown. This study aims to investigate METTL3- and ALKBH5-mediated m6A modification function and mechanism in NTDs. Herein, our results demonstrate that SAM play not only a compensatory role, it also leads to changes of m6A modification in neural tube development and regulation. Additionally, these data implicate that METTL3 is enriched in HT-22 cells, and METTL3 knockdown reduces cell proliferation and increases apoptosis through suppressing Wnt/β-catenin signaling pathway. Significantly, overexpression of ALKBH5 can only inhibit cell proliferation, but cannot promote cell apoptosis. This research reveals an important role of SAM in development of NTDs, providing a good theoretical basis for further research on NTDs. This finding represents a novel epigenetic mechanism underlying that the m6A modification has profound and lasting implications for neural tube development.

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