Discontinuity of primary and secondary neural tube in spina bifida induced by retinoic acid in mice

Teratology ◽  
1990 ◽  
Vol 41 (3) ◽  
pp. 257-274 ◽  
Author(s):  
Yoshiko Yasuda ◽  
Hiroyoshi Konishi ◽  
Takahide Kihara ◽  
Takashi Tanimura
Keyword(s):  
Retinoic Acid ◽  
Spina Bifida ◽  
Neural Tube

scholarly journals Bhlhe40/Sirt1 Axis-Regulated Mitophagy Is Implicated in All-Trans Retinoic Acid-Induced Spina Bifida Aperta

2021 ◽  
Vol 9 ◽  
Author(s):  
Lu Zhao ◽  
Dan Liu ◽  
Wei Ma ◽  
Hui Gu ◽  
Xiaowei Wei ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Spina Bifida ◽  
Neural Tube ◽  
Molecular Mechanisms ◽  
Underlying Mechanism ◽  
Neural Tube Closure ◽  
Luciferase Reporter ◽  
All Trans Retinoic Acid ◽  
Spina Bifida Aperta ◽  
First Time

Neural tube defects (NTDs) are the most severe congenital malformations that result from failure of neural tube closure during early embryonic development, and the underlying molecular mechanisms remain elusive. Mitophagy is the best-known way of mitochondrial quality control. However, the role and regulation of mitophagy in NTDs have not yet been elucidated. In this study, we used an all-trans retinoic acid (ATRA)-induced rat model to investigate mitophagy and its underlying mechanism in spina bifida aperta (SBA). The results of western blot, immunofluorescence and RT-qPCR analyses indicated that mitophagy was impaired and Sirt1 was downregulated in SBA. Administration of resveratrol-a strong specific Sirt1 activator-activated Sirt1, thus attenuating autophagy suppression and ameliorating SBA. RNA-sequencing and bioinformatics analysis results indicated that transcriptional regulation played an important role in NTDs. A luciferase reporter assay was performed to demonstrate that the transcription factor Bhlhe40 directly bound to and negatively regulated Sirt1 expression. Further, we discovered that the Bhlhe40/Sirt1 axis regulated mitophagy in neural stem cells. Collectively, our results for the first time demonstrate that Bhlhe40/Sirt1 axis regulated mitophagy is implicated in ATRA-induced SBA. Our findings provide new insights into pathogenesis of NTDs and a basis for potential therapeutic targets for NTDs.

Detection of spina bifida in the first trimester of gestation in association with triploidy

2017 ◽  
Author(s):  
K.K. Otaryan , C.G. Gagaev
Keyword(s):  
Spina Bifida ◽  
Early Detection ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
First Trimester ◽  
Termination Of Pregnancy ◽  
Diagnostic Tools ◽  
Prenatal Detection ◽  
Post Abortion

The case of prenatal detection of spina bifida at 12+3 weeks of gestation is described. Termination of pregnancy was performed at 13+3 weeks. Post-abortion karyotyping revealed triploidy (69XXX). Diagnostic tools for early detection of neural tube defects in the 1st trimester of gestation and subsequent appropriate management of pregnancy are discussed.

scholarly journals Secondary Myelitis in Dermal Sinus Causing Paraplegia in a Child with Previously Normal Neurological Function

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Sakina Rashid ◽  
Grace Kinabo ◽  
Marissa Kellogg ◽  
William P. Howlett ◽  
Marieke C. J. Dekker
Keyword(s):  
Congenital Anomaly ◽  
Spina Bifida ◽  
Neural Tube ◽  
Clinical Course ◽  
Acute Infection ◽  
Early Embryogenesis ◽  
The Other ◽  
Neurological Deficits ◽  
Dermal Sinus ◽  
Neurological Development

Neural tube defects result from failure of neural tube fusion during early embryogenesis, the fourth week after conception. The spectrum of severity is not uniform across the various forms of this congenital anomaly as certain presentations are not compatible with extrauterine life (anencephaly) while, on the other hand, other defects may remain undiagnosed as they are entirely asymptomatic (occult spina bifida). We report a child with previously normal neurological development, a devastating clinical course following superinfection of a subtle spina bifida defect which resulted in a flaccid paralysis below the level of the lesion and permanent neurological deficits following resolution of the acute infection and a back closure surgery.

Retinoid-binding protein distribution in the developing mammalian nervous system

Development ◽  
1990 ◽  
Vol 109 (1) ◽  
pp. 75-80 ◽  
Author(s):  
M. Maden ◽  
D.E. Ong ◽  
F. Chytil
Keyword(s):  
Nervous System ◽  
Retinoic Acid ◽  
Neural Crest ◽  
Motor Neurons ◽  
Neural Tube ◽  
Binding Protein ◽  
Sympathetic Ganglia ◽  
Retinol Binding Protein ◽  
Otic Vesicle ◽  
Protein Distribution

We have analysed the distribution of cellular retinol-binding protein (CRBP) and cellular retinoic acid-binding protein (CRABP) in the day 8.5-day 12 mouse and rat embryo. CRBP is localised in the heart, gut epithelium, notochord, otic vesicle, sympathetic ganglia, lamina terminalis of the brain, and, most strikingly, in a ventral stripe across the developing neural tube in the future motor neuron region. This immunoreactivity remains in motor neurons and, at later stages, motor axons are labelled in contrast to unlabelled sensory axons. CRABP is localised to the neural crest cells, which are particularly noticeable streaming into the branchial arches. At later stages, neural crest derivatives such as Schwann cells, cells in the gut wall and sympathetic ganglia are immunoreactive. An additional area of CRABP-positive cells are neuroblasts in the mantle layer of the neural tube, which subsequently appear to be the axons and cell bodies of the commissural system. Since retinol and retinoic acid are the endogenous ligands for these binding proteins, we propose that retinoids may play a role in the development and differentiation of the mammalian nervous system and may interact with certain homoeobox genes whose transcripts have also been localised within the nervous system.

scholarly journals CIC missense variants contribute to susceptibility for spina bifida

2021 ◽  
Author(s):  
Xiao Han ◽  
Xuanye Cao ◽  
Vanessa Aguiar-Pulido ◽  
Wei Yang ◽  
Menuka Karki ◽  
...  
Keyword(s):  
Spina Bifida ◽  
Cell Line ◽  
Neural Tube ◽  
Folate Receptor ◽  
Spinocerebellar Ataxia Type ◽  
Loss Of Function ◽  
Missense Variants ◽  
Increased Risk ◽  
Cell Line Hela

Neural Tube Defects (NTDs) are congenital malformations resulting from abnormal embryonic development of the brain, spine, or spinal column. The genetic etiology of human NTDs remains poorly understood despite intensive investigation. CIC, homolog of the Capicua transcription repressor, has been reported to interact with ataxin-1 (ATXN1) and participate in the pathogenesis of spinocerebellar ataxia type 1. Our previous study demonstrated that CIC loss of function (LoF) variants contributed to cerebral folate deficiency by downregulating folate receptor 1 (FOLR1) expression. Given the importance of folate transport in neural tube formation, we hypothesized that CIC variants could contribute to increased risk for NTDs by depressing embryonic folate concentrations. In this study, we examined CIC variants from whole genome sequencing (WGS) data of 140 isolated spina bifida cases and identified 8 missense variants of CIC gene. We tested the pathogenicity of the observed variants through multiple in vitro experiments. We determined that CIC variants decreased FOLR1 protein level and planar cell polarity (PCP) pathway signaling in a human cell line (HeLa). In a murine cell line (NIH3T3), CIC loss of function variants down regulated PCP signaling. Taken together, this study provides evidence supporting CIC as a risk gene for human NTD.

scholarly journals Mengenal Spina Bifida dan Pencegahannya

2021 ◽  
Vol 1 (12) ◽  
pp. 896-903
Author(s):  
Genta Faesal Atsani ◽  
Zanetha Mauly Ilawanda ◽  
Ilma Fahira Basyir
Keyword(s):  
Spina Bifida ◽  
Birth Defects ◽  
Neural Tube ◽  
Neural Tube Defects ◽  
Congenital Abnormality ◽  
Congenital Abnormalities ◽  
Folic Acid Supplementation ◽  
Online Portal ◽  
The Brain ◽  
Developing Spinal Cord

Neural tube defects (NTD) are one of the birth defects or congenital abnormalities that occur in the brain and spine, and commonly find in newborns worldwide. Anencephaly and spina bifida are the two prevalent forms of NTD. The incidence of spina bifida happen on average 1 in 1000 cases of birth worldwide and there are 140,000 cases per year worldwide. Source searches were carried out on the online portal of journal publications as many as 20 sources from MedScape, Google Scholar and the Nation Center for Biotechnology Information / NCBI with the keywords “Neural tube defects (NTD), prevention, and spina bifida”. Spina bifida is a congenital abnormality that occurs in the womb due to a failure of closing process the neural tube during the first few weeks of embryonic development which causes the spine not completely close around the developing spinal cord nerves. NTD can ensue multifactorial conditions such as genetic, environmental, and folate deficiency. The use of folic acid supplementation starting at least 3 months before pregnancy, those are 400 mcg (0.4 mg) per day and 800 mcg per day during pregnancy can reduce the risk of developing neural tube defects such as spina bifida. Generally, spina bifida is undertaking by surgery and the regulation of patients comorbid. Public can find out prevention to avoid or reduce the risk of spina bifida so that the incidence of spina bifida can decrease along with the increasing awareness of the community regarding this disease.

Novel retinoic acid generating activities in the neural tube and heart identified by conditional rescue of Raldh2 null mutant mice

Development ◽  
2002 ◽  
Vol 129 (9) ◽  
pp. 2271-2282 ◽  
Author(s):  
Felix A. Mic ◽  
Robert J. Haselbeck ◽  
Arnold E. Cuenca ◽  
Gregg Duester
Keyword(s):  
Spinal Cord ◽  
Retinoic Acid ◽  
Neural Tube ◽  
The Novel ◽  
Vertebrate Development ◽  
Targeted Disruption ◽  
Surface Ectoderm ◽  
Eye Field ◽  
Null Mutant Mice ◽  
Dorsal Retina

Retinoid control of vertebrate development depends upon tissue-specific metabolism of retinol to retinoic acid (RA). The RA biosynthetic enzyme RALDH2 catalyzes much, but not all, RA production in mouse embryos, as revealed here with Raldh2 null mutants carrying an RA-responsive transgene. Targeted disruption of Raldh2 arrests development at midgestation and eliminates all RA synthesis except that associated with Raldh3 expression in the surface ectoderm of the eye field. Conditional rescue of Raldh2–/– embryos by limited maternal RA administration allows development to proceed and results in the establishment of additional sites of RA synthesis linked to Raldh1 expression in the dorsal retina and to Raldh3 expression in the ventral retina, olfactory pit and urinary tract. Unexpectedly, conditionally rescued Raldh2–/– embryos also possess novel sites of RA synthesis in the neural tube and heart that do not correspond to expression of Raldh1-3. RA synthesis in the mutant neural tube was localized in the spinal cord, posterior hindbrain and portions of the midbrain and forebrain, whereas activity in the mutant heart was localized in the conotruncus and sinus venosa. In the posterior hindbrain, this novel RA-generating activity was expressed during establishment of rhombomeric boundaries. In the spinal cord, the novel activity was localized in the floorplate plus in the intermediate region where retinoid-dependent interneurons develop. These novel RA-generating activities in the neural tube and heart fill gaps in our knowledge of how RA is generated spatiotemporally and may, along with Raldh1 and Raldh3, contribute to rescue of Raldh2–/– embryos by producing RA locally.

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