This study is to assess the prevalence rates spatial pattern of neural tube defects with geographic information system and spatial filtering technique. A total of 80 infants who diagnosed from neural tube defects in t...This study is to assess the prevalence rates spatial pattern of neural tube defects with geographic information system and spatial filtering technique. A total of 80 infants who diagnosed from neural tube defects in the area being studied between 1998 and 2001 were analyzed. Firstly, the geographic information system （GIS） software ArcGIS was used to map the crude prevalence rates. Secondly, the data were smoothed by the method of spatial filtering. We evaluated that the effect of changes in spatial filtering radius size was assessed by creating maps based on various filtering radius sizes. The 3 miles or larger filtering radius gives better section variability than the 2 and 2.5 miles or smaller ones. The maps produced by the spatial filtering technique indicate that prevalence rates in the villages in the southeastern region are to produce higher prevalence than that in the other regions. The smoothed maps based on Heshun County display a more adequate data representation than the raw prevalence rate map.展开更多
Objective Our objective is to build a model that explains the association between the exposure to trace elements in the soil and the risk of neural tube defects. Methods We built a function with different parameters t...Objective Our objective is to build a model that explains the association between the exposure to trace elements in the soil and the risk of neural tube defects. Methods We built a function with different parameters to describe the effects of trace elements on neural tube defects. The association between neural tube defects and trace element levels was transformed into an optimization problem using the maximum likelihood method. Results Tin, lead, nickel, iron, copper, and aluminum had typical layered effects （dosage effects） on the prevalence of neural tube defects. Arsenic, selenium, zinc, strontium, and vanadium had no effect, and molybdenum had one threshold value that affected the prevalence of birth defects. Conclusion As an exploratory research work, our model can be used to determine the direction of the effect of the trace element content of cultivated soil on the risk of neural tube defects, which shows the clues by the dosage effect of their toxicological characteristics. Based on our findings, future biogeochemical research should focus on the direct effects of trace elements on human health.展开更多
Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube developme...Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube development, C57BL/6 female mice were fed for 4 weeks with com- mercial food containing 3% advanced glycation end product bovine serum albumin （AGE-BSA） or 3% bovine serum albumin （BSA） as a control. After mating mice, oxidative stress markers including malondialdehyde and H202 were measured at embryonic day 7.5 （E7.5） of ges- tation, and the level of intracellular reactive oxygen species （ROS） in embryonic cells was determined at E8.5. In addition to evaluating NTDs, an enzyme-linked immunosorbent assay was used to determine the effect of embryonic protein administration on the N-（carboxymethyl） lysine reactivity of acid and carboxyethyl lysine antibodies at E10.5. The results showed a remarkable increase in the incidence of NTDs at El0.5 in embryos of mice fed with AGE-BSA （no hyperglycemia） compared with control mice. Moreover, embryonic protein administration resulted in a noticeable increase in the reactivity of N-（carboxymethyl） lysine and N（ε）-（carboxyethyl） lysine antibodies. Malondialdehyde and H2O2 levels in embryonic cells were increased at E7.5, followed by increased intracellular ROS levels at E8.5. Vitamin E supplementation could partially recover these phenomena. Collectively, these results suggest that AGE-BSA could induce NTDs in the absence of hyperglycemia by an underlying mechanism that is at least partially associated with its capacity to increase embryonic oxidative stress levels.展开更多
Objective To study the prevalence of different types of neural tube defects （NTDs） in Luliang Prefecture, Shanxi province, where the prevalence of NTDs is unusually high and the correlation between NTDs prevalence a...Objective To study the prevalence of different types of neural tube defects （NTDs） in Luliang Prefecture, Shanxi province, where the prevalence of NTDs is unusually high and the correlation between NTDs prevalence and patterns. Methods A surveillance population-based birth defects was performed in Luliang Prefecture, Shanxi province. Results The results of our study showed that the prevalence of NTDs was 2-fold higher in Luliang Prefecture than in other areas of Shanxi province. Unusual patterns of NTDs were found, however, multiple NTDs were relatively common in Luliang Prefecture, accounting for over 13% of all NTDs cases in China. Conclusion The prevalence of NTDs is associated with its patterns.展开更多
In the field of developmental neurobiology, accurate and ordered regulation of the cell cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified s...In the field of developmental neurobiology, accurate and ordered regulation of the cell cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified several genes involved in the development of neural tube defects. In this study, we established a model of developmental neural tube defects by administration of retinoic acid to pregnant rats. Gene chip hybridization analysis showed that genes related to the cell cycle and apoptosis, signal transduction, transcription and translation regulation, energy and metabolism, heat shock, and matrix and cytoskeletal proteins were all involved in the formation of developmental neural tube defects. Among these, cell cycle-related genes were predominant. Retinoic acid treat-ment caused differential expression of three cell cycle-related genes p57kip2, Cdk5 and Spin, the expression levels of which were downregulated by retinoic acid and upregulated during normal neural tube formation. The results of this study indicate that cell cycle-related genes play an im-portant role in the formation of neural tube defects. P57kip2, Cdk5 and Spin may be critical genes in the pathogenesis of neural tube defects.展开更多
Objective: To estimate the prevalence rates of neural tube defects (NTDs) in Heshun County, Shanxi Province, China by Bayesian smoothing technique. Methods: A total of 80 infants in the study area who were diagnosed w...Objective: To estimate the prevalence rates of neural tube defects (NTDs) in Heshun County, Shanxi Province, China by Bayesian smoothing technique. Methods: A total of 80 infants in the study area who were diagnosed with NTDs were analyzed. Two mapping techniques were then used. Firstly, the GIS software ArcGIS was used to map the crude prevalence rates. Secondly, the data were smoothed by the method of empirical Bayes estimation. Results: The classical statistical approach produced an extremely dishomogeneous map, while the Bayesian map was much smoother and more interpretable. The maps produced by the Bayesian technique indicate the tendency of villages in the southeastern region to produce higher prevalence or risk values. Conclusions: The Bayesian smoothing technique addresses the issue of heterogeneity in the population at risk and it is therefore recommended for use in explorative mapping of birth defects. This approach provides procedures to identify spatial health risk levels and assists in generating hypothesis that will be investigated in further detail.展开更多
To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatography-mass spectrometry with stable isoto...To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatography-mass spectrometry with stable isotope of MMA as an internal standard. Amniotic fluid and maternal urine MMA concentration, maternal serum folate, red blood cell folate and vitamin B 12 levels were measured in the middle term of NTD-affected and normal pregnancies. Amniotic fluid and maternal urine MMA concentrations in the middle term of NTD affected pregnancies (1.4±0.9 μmol/L, and 22.1±12.6 nmol/μmol creatinine) were significantly higher than that of normal pregnancies (1.0±0.4μmol/L, and 2.5±1.1 nmol/μmol creatinine). There was no significant difference between normal and NTD pregnancies for serum folate, red blood cell folate and vitamin B 12 levels. The results suggested that MMAs in amniotic fluid and maternal urine are sensitive markers for early diagnosis of NTD. Vitamin B 12 is an active cofactor involved in the remethylation of homocycteine and its deficiency is an independent risk factor for NTD. MMA is a specific and sensitive marker for intracellular vitamin B 12 deficiency. This study suggests that it is necessary to monitor the vitamin B 12 deficiency and advocates vitamin B 12 supplementation with folate prevention program.展开更多
The present study involved a questionnaire survey of 156 mothers that gave birth to children with neural tube defects or had a history of pregnancy resulting in children with neural tube defects （case group） and 156...The present study involved a questionnaire survey of 156 mothers that gave birth to children with neural tube defects or had a history of pregnancy resulting in children with neural tube defects （case group） and 156 control mothers with concurrent healthy children （control group） as well as detection of mitochondrial membrane transporter protein gene [uncoupling protein 2 （UCP2）] polymorphism. The maternal UCP2 3＇ untranslated region （UTR） D/D genotype and D allele frequency were significantly higher in the case group compared with the control group （odds ratio （OR） 3.233; 95% confidence interval （C/） 1.103 9.476; P= 0.040; OR： 3.484; 95% CI： for neural tube defects 2.109 5.753; P 〈 0.001）. Univariate and multivariate logistic regression analysis of risk factors for neural tube defects showed that a matemal UCP2 3＇ UTR D/D genotype was negatively interacted with the mothers＇ consumption of frequent fresh fruit and vegetables （S = 0.007）, positively interacted with the mothers＇ frequency of germinated potato consumption （S = 2.15） and positively interacted with the mothers＇ body mass index （S = 3.50）. These findings suggest that maternal UCP2 3＇ UTR gene polymorphism, pregnancy time, consumption of germinated potatoes and body mass index are associated with an increased risk for neural tube defects in children from mothers living in Shanxi province, China. Moreover, there is an apparent gene-environment interaction involved in the development of neural tube defects in offspring.展开更多
Several studies have demonstrated that Slug,which encodes a zinc finger of the Snail family of transcription factors,is a potential risk factor for neural tube defects.Neural tube defects tend to occur with a high rat...Several studies have demonstrated that Slug,which encodes a zinc finger of the Snail family of transcription factors,is a potential risk factor for neural tube defects.Neural tube defects tend to occur with a high rate in Shanxi province,China.The present case-control study investigated genotypic distributions and allele frequencies of Slug C1548A polymorphisms in DNA samples from59 women with a history of neural tube defect pregnancies and 73 controls during the same period from Shanxi Province,China.Results demonstrated that women with a history of neural tube defect pregnancies had significantly greater genotypic distributions of Slug AA genotypes and A allele frequencies compared with controls,and A allele Slug C1548A was a risk factor for neural tube defects（odds ratio = 3.444;95% confidence interval;2.021-5.868,P 〈 0.05）.Three-dimensional structure prediction revealed that Slug C1548A resulted in transition of aspartic acid into glutamate at position 119.This indicated that these mutations could lead to damaged protein structure and function.These findings suggest that Slug C1548A gene polymorphism is closely related to neural tube defects in a population of Han Chinese origin from Shanxi Province,China展开更多
BACKGROUND： Neural tube defects can be induced by abnormal factors in vivo or in vitro during development. However, the molecular mechanisms of neural tube defect induction, and the related gene expression and regula...BACKGROUND： Neural tube defects can be induced by abnormal factors in vivo or in vitro during development. However, the molecular mechanisms of neural tube defect induction, and the related gene expression and regulation are still unknown. OBJECTIVE： To compare the differences in gene expression between normal embryos and those with neural tube defects. DESIGN, TIME AND SETTING： A neural development study was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA between January 2006 and October 2007. MATERIALS： Among 120 adult Kunming mice, 60 pregnant mice were randomly and evenly divided into a retinoic acid group （n = 30） and a normal control group （n =30）. The retinoic acid was produced by Sigma, USA, the gene microarray by the Amersham Pharmacia Company, Hong Kong, and the gene sequence was provided by the Incyte database, USA. METHODS： Retinoic acid was administered to prepare models of neural tube defects, and corn oil was similarly administered to the normal control group. Total RNA was extracted from embryonic tissue of the two groups using a Trizol kit, and a cDNA microarray containing 1 100 known genes was used to compare differences in gene expression between the normal control group and the retinoic acid group on embryonic （E） day 10.5 and 11.5. Several differentially expressed genes were randomly selected from the two groups for Northern blotting, to verify the results of the cDNA microarray. MAIN OUTCOME MEASURES： Morphological changes and differential gene expression between the normal control group and the retinoic acid group. RESULTS： Anatomical microscopy demonstrated that an intact closure of the brain was formed in the normal mouse embryos by days E10.5 and E11.5. The cerebral appearance was full and smooth, and the surface of the spine was intact. However, in the retinoic acid group on days E10.5 and E11.5, there were more dead embryos. Morphological malformations typically included non-closure at the top of the cranium and abnormal changes of the metencephalon and face. cDNA microarray analysis suggested that the changes in expression of seven different genes were similar on both days E10.5 and E11.5. These were downregulation of NekT, Igfbp5, Zw10, Csf3r, Psmc6 and Rb 1, and upregulation of Apoa-4. This study also indicated that Cdk5 expression was downregulated in the retinoic acid group on day E11.5. The results of the cDNA microarray analysis were partly confirmed by Northern blotting. CONCLUSION： Cdk5, Nek7, Igfbp5, Zw10, Csf3r, Psmc6, Rb1 and Apoa-4 may be key factors in retinoic acid-induced neural tube defects.展开更多
<b><span style="font-family:;" "="">Background:</span></b><span style="font-family:;" "=""> As C677T mutation, A1298C mutation in methyle...<b><span style="font-family:;" "="">Background:</span></b><span style="font-family:;" "=""> As C677T mutation, A1298C mutation in methylene tetrahydrofolate reductase (MTHFR) gene results in a decreased MTHFR activity but </span><span style="font-family:;" "="">to</span><span style="font-family:;" "=""> a less extent, it is known as a risk factor of predisposition to human neural tube defects (NTDs), in some populations. Our objective was therefore to study, for the first time in Algerian population, if A1298C polymorphism confer</span><span style="font-family:;" "="">s </span><span style="font-family:;" "="">risk for the occurrence of this abnormality. We have examined the distribution of the genotype and the allele frequencies of A1298C mutation, and also their influence on plasma homocysteine (Hcy) concentration. <b>Patients and Methods:</b> We studied this polymorphism in 38 mothers of NTD cases and 67 control individuals of an eastern Algerian population. The muta<span>tion was determined by polymerase chain reaction</span></span><span style="font-family:;" "="">-</span><span style="font-family:;" "="">restriction fragm</span><span style="font-family:;" "="">ent length polymorphism analysis (PCR/RFLP). Plasma homocysteine concentration was analyzed using an automated chemiluminescence method. <b>Results:</b> No signi?cant association could be observed between allele and genotypes frequencies of A1298C MTHFR gene polymorphism and NTDs risk. However, we could observe that A1298C polymorphism affects homocysteine metabolism in mothers of NTD cases leading to homocysteine concentration values higher in AA genotype and lower in AC/CC genotypes (15.29</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">±</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">11.8 μmol/l <span>vs.<i> </i></span>8.63</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">±</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">3.83 μmol/l, <i>p</i> < 0.05). <b>Conclusion:</b> Data indicate that A1298C MTHFR gene polymorphism might be a risk factor by affecting homocysteine metabolism in mothers of Algerian children with NTDs.</span>展开更多
Abstract Objective To develop a new technique for assessing the risk of birth defects, which are a major cause of infant mortality and disability in many parts of the world. Methods The region of interest in this stud...Abstract Objective To develop a new technique for assessing the risk of birth defects, which are a major cause of infant mortality and disability in many parts of the world. Methods The region of interest in this study was Heshun County, the county in China with the highest rate of neural tube defects （NTDs）. A hybrid particle swarm optimization/ant colony optimization （PSO/ACO） algorithm was used to quantify the probability of NTDs occurring at villages with no births. The hybrid PSO/ACO algorithm is a form of artificial intelligence adapted for hierarchical classification. It is a powerful technique for modeling complex problems involving impacts of causes. Results The algorithm was easy to apply, with the accuracy of the results being 69.5%＋7.02% at the 95% confidence level. Conclusion The proposed method is simple to apply, has acceptable fault tolerance, and greatly enhances the accuracy of calculations.展开更多
Background The 5,10-methylenetetrahydrofolate reductase （MTHFR） and methionine synthase （MS） are attractive candidates for screening for risk of neural tube defects （NTDs）. The aim of the current study was to in...Background The 5,10-methylenetetrahydrofolate reductase （MTHFR） and methionine synthase （MS） are attractive candidates for screening for risk of neural tube defects （NTDs）. The aim of the current study was to investigate maternal MTHFR and MS polymorphisms and the interaction between them and their influence on children with NTDs in the Shanxi Province of northern China. Methods Fifty-one mothers who previously had children with NTDs constituted the case group and 51 age-matched mothers with children that were unaffected by any birth defects constituted the control group. All subjects were genotyped for MTHFR C677T and MS A2756G polymorphisms. SPSS 11.5 software package was used for all analyses. Results There was a significant difference for MTHFR genotype distribution for one site （C677T） between the case and control groups. The T allele frequencies were significantly higher in the case group than in the control group （55.9% vs. 35.3%, P 〈0.05）. A lack of association was observed for the MS A2756G polymorphism. There was an interaction between the maternal MTHFR C677T genotype and MS A2756G genotype. Conclusion Genetic interaction between MTHFR and MS genes raises the probability of neural tube defects.展开更多
Background Maternal exposure to nitrate, nitrite, and N-nitroso compounds from drinking water or diet has been associated with an increased risk of neural tube defects （NTDs） in some studies. Pickled vegetables cont...Background Maternal exposure to nitrate, nitrite, and N-nitroso compounds from drinking water or diet has been associated with an increased risk of neural tube defects （NTDs） in some studies. Pickled vegetables contain relatively large amounts of nitrite and N-nitroso compounds. We examined the association between maternal periconceptional consumption of pickled vegetables and NTDs in Shanxi Province of northern China. Methods Data were derived from a population based case-control study of major external birth defects in four counties of $hanxi Province. Participants included 519 NTDs cases identified between 2003 and 2007 and 694 healthy controls. Exposure information was collected within 1 week after delivery. Multivariable non-conditioanal Logistic regression model was used to estimate the adjusted odds ratio （OR） controlling for potential confounding variables.展开更多
Background Neural tube defects are the most common human birth defects. The causes are multifactorial with complex genetic and environmental factors, although the exact genetic causes are unknown. This research was co...Background Neural tube defects are the most common human birth defects. The causes are multifactorial with complex genetic and environmental factors, although the exact genetic causes are unknown. This research was conducted to study the frequency of Msx2 gene polymorphisms in 59 women with a history of pregnancy with a neural tube defect and in 73 healthy controls. We aimed to determine the effect of this genetic polymorphism on the incidence of neural tube defects in the Han Chinese population.Methods We studied 59 mothers with at least one previous child with a neural tube defect （the case group） and 73case-control subjects during the same period, from Shanxi Province, China. We analyzed the genotypic distributions and allele frequencies of Msx2 C386T poiymorphisms in DNA samples from the case and control groups. A three-dimensional protein model was predicted using Swiss-Pdb Viewer software version 4.0. Disease association was analyzed using chi-square tests.Results Significant differences were observed in the genotypes and allele frequencies of the Msx2 C386T allele between the case and control groups （CT： 32% vs. 15%, P=0.0073 and TT 15% vs. 4%, P=0.013, respectively）. Logistic regression analysis showed that the C386T mutation is a potential risk factor for neural tube defects （P 〈0.05; OR： 3.466;95%CI： 1.831-6.560）. Three-dimensional structure prediction revealed that the Msx2 C386T mutation results in a threonine substitution for methionine at position 129 of exon 2, which might lead to structural mutations or dysfunctions in the protein encoded by Msx2.Conclusion Maternal Msx2 C386T gene polymorphisms were associated with fetal neural tube defects in Han Chinese women in Shanxi Province.展开更多
The protein composition of cerebrospinal fluid（CSF） in neural tube defects（NTDs） remains unknown. We investigated the protein composition of CSF from 9 infants with NTDs using isobaric tags for relative and absolu...The protein composition of cerebrospinal fluid（CSF） in neural tube defects（NTDs） remains unknown. We investigated the protein composition of CSF from 9 infants with NTDs using isobaric tags for relative and absolute quantitation（iTRAQ）. We identified 568 proteins in the CSF of infants with spina bifida, which is the most common type of NTD. Among these, 18 proteins were associated with neural tube closure in the CSF during human embryonic neurulation and 5 were involved in NTDs. Based on these results, an animal model was further utilized to investigate early serum biomarkers for NTDs.We found that the myristoylated alanine-rich C-kinase substrate, Kunitz-type protease inhibitor 2, andapolipoprotein B-100 protein levels were decreased in both embryos and the sera of pregnant Sprague-Dawley rats carrying embryos with NTDs. CSF proteins may be useful in the discovery of potential serum biomarkers for NTDs.展开更多
Neural tube defects （NTDs） are a group of birth anomalies having a profound physical, emotional, and financial effects on families and communities. Their etiology is complex, involving environmental and genetic fact...Neural tube defects （NTDs） are a group of birth anomalies having a profound physical, emotional, and financial effects on families and communities. Their etiology is complex, involving environmental and genetic factors that interact to modulate the incidence and severity of the developing phenotype. The planar cell polarity （PCP） pathway controls the process of convergent extension （CE） during gastrulation and neural tube closure and has been implicated in the pathogenesis of NTDs in animal models and human cohorts. This review summarizes the cumulative results of recent studies on PCP signaling pathway and human NTDs. These results demonstrate that PCP gene alterations contribute to the etiology of human NTDs.展开更多
To date, little information has been available regarding genes involved in the regulation of embryonic cell development, which participate in retinoic acid-induced neural tube defects in mice. Previous studies have re...To date, little information has been available regarding genes involved in the regulation of embryonic cell development, which participate in retinoic acid-induced neural tube defects in mice. Previous studies have revealed seven differentially expressed genes involved in neural tube developmental defects. However, gene expression and regulation is a complex process. Therefore, gene expression differences between normal and defective neural tubes at 9.5 and 10.5 days were compared. A total of eight differentially expressed genes exhibited coincident alterations at embryonic 9.5 and 10.5 days. In mice with retinoic acid-induced neural tube defects, NeK7, IGFBP5 ZW10, Csf3r, PSMC6, Cdk5, and Rbl expressions were downregulated, but Apoa-4 expression was upregulated. These results were confirmed by Northern blot hybridization. Results suggested that NeK7, IGFBP5, ZW10, Csf3r, PSMC6, Cdk5, Rb1, and Apoa-4 are important regulatory factors involved in neural tube defects.展开更多
Background:The sonic hedgehog(SHH)pathway is an important signaling pathway for neural tube closure.GLI family zinc finger 2(GLI2)is the major activation mediator of the SHH pathway;however,no single-nucleotide polymo...Background:The sonic hedgehog(SHH)pathway is an important signaling pathway for neural tube closure.GLI family zinc finger 2(GLI2)is the major activation mediator of the SHH pathway;however,no single-nucleotide polymorphisms(SNPs)in GLI2 have been reported to be associated with human neural tube defects(NTDs)to date.Here,we evaluated a mutation in GLI2 in the Han Chinese population.Methods:We used SNPscan to genotype rs3738880 in the GLI2 coding region.We then investigated the function of this gene by Western blotting and dual-luciferase assays.Results:In this study,we found that the GLI2 missense variant rs3738880 significantly increased the risk of NTDs in the Han Chinese population via association studies in a cohort of 254 patients and 277 controls from Shanxi Province(odds ratio[OR]=1.89,95%confidence interval[CI]=1.28-2.80,P=0.0012).Additional stratified analyses demonstrated that rs3738880 was significantly related to spina bifida(114 cases,OR=2.01,95%CI=1.19–3.38,P=0.0067).Functional analysis revealed that rs3738880 did not affect GLI2 protein stability and significantly increased SHH activity because of the introduction of a potential phosphorylation site in GLI2.Conclusion:rs3738880 was a risk factor for NTDs in the Han Chinese population.展开更多
Neural tube defects （NTDs） are severe congenital malformation diseases, which occur in 1 out of 1000 births in human. In Xenopus, several tissue movements are involved in the neural tube closure process. Immediately...Neural tube defects （NTDs） are severe congenital malformation diseases, which occur in 1 out of 1000 births in human. In Xenopus, several tissue movements are involved in the neural tube closure process. Immediately after the neural tube fusion, the neural crest cells get monopolar protrusion toward dorsal midline and migrate to form the roof of the neural tube. At the same time, radial intercalation takes place from the ventral neural tube and forces it to be single-layered. Here, we physically block the neural tube closure to test the cell movements and the following patterning in Xenopus laevis explants. The results show that the single-layered neural tube fails to form and the neural crest cells remain at the lateral regions in the explants with NTDs. However, the patterning of the neural tube is not affected as indicated by the normal expression of the preneural genes. These results indicate a requirement of the neural tube fusion for the radial intercalation and the dorsal midline directed neural crest migration, but not for the dorsal-ventral patterning of the neural tube.展开更多
基金Supported by the National Basic Reserch Program of China (973 Program) (2001CB5103)the National Natural Science Foundation of China (40471111 and 70571076).
文摘This study is to assess the prevalence rates spatial pattern of neural tube defects with geographic information system and spatial filtering technique. A total of 80 infants who diagnosed from neural tube defects in the area being studied between 1998 and 2001 were analyzed. Firstly, the geographic information system （GIS） software ArcGIS was used to map the crude prevalence rates. Secondly, the data were smoothed by the method of spatial filtering. We evaluated that the effect of changes in spatial filtering radius size was assessed by creating maps based on various filtering radius sizes. The 3 miles or larger filtering radius gives better section variability than the 2 and 2.5 miles or smaller ones. The maps produced by the spatial filtering technique indicate that prevalence rates in the villages in the southeastern region are to produce higher prevalence than that in the other regions. The smoothed maps based on Heshun County display a more adequate data representation than the raw prevalence rate map.
基金supported by the National "973" project on Population and Health (No. 2007CB5119001)the National Yang‐Zi Scholar Program, 211 and 985 projects of Peking University (No. 20020903)
文摘Objective Our objective is to build a model that explains the association between the exposure to trace elements in the soil and the risk of neural tube defects. Methods We built a function with different parameters to describe the effects of trace elements on neural tube defects. The association between neural tube defects and trace element levels was transformed into an optimization problem using the maximum likelihood method. Results Tin, lead, nickel, iron, copper, and aluminum had typical layered effects （dosage effects） on the prevalence of neural tube defects. Arsenic, selenium, zinc, strontium, and vanadium had no effect, and molybdenum had one threshold value that affected the prevalence of birth defects. Conclusion As an exploratory research work, our model can be used to determine the direction of the effect of the trace element content of cultivated soil on the risk of neural tube defects, which shows the clues by the dosage effect of their toxicological characteristics. Based on our findings, future biogeochemical research should focus on the direct effects of trace elements on human health.
基金supported by the grant from Shaanxi Technology Committee of China,No.2013JM4001the China Scholarship Council(CSC)
文摘Our previous study showed an association between advanced glycation end products （AGEs） and neural tube defects （NTDs）. To understand the molecular mechanisms underlying the effect of AGEs on neural tube development, C57BL/6 female mice were fed for 4 weeks with com- mercial food containing 3% advanced glycation end product bovine serum albumin （AGE-BSA） or 3% bovine serum albumin （BSA） as a control. After mating mice, oxidative stress markers including malondialdehyde and H202 were measured at embryonic day 7.5 （E7.5） of ges- tation, and the level of intracellular reactive oxygen species （ROS） in embryonic cells was determined at E8.5. In addition to evaluating NTDs, an enzyme-linked immunosorbent assay was used to determine the effect of embryonic protein administration on the N-（carboxymethyl） lysine reactivity of acid and carboxyethyl lysine antibodies at E10.5. The results showed a remarkable increase in the incidence of NTDs at El0.5 in embryos of mice fed with AGE-BSA （no hyperglycemia） compared with control mice. Moreover, embryonic protein administration resulted in a noticeable increase in the reactivity of N-（carboxymethyl） lysine and N（ε）-（carboxyethyl） lysine antibodies. Malondialdehyde and H2O2 levels in embryonic cells were increased at E7.5, followed by increased intracellular ROS levels at E8.5. Vitamin E supplementation could partially recover these phenomena. Collectively, these results suggest that AGE-BSA could induce NTDs in the absence of hyperglycemia by an underlying mechanism that is at least partially associated with its capacity to increase embryonic oxidative stress levels.
基金supported by the Major State Basic Research and Development Program of China "973 Program" (No.2007CB511901)special for National Postdoctoral fund (200801016)+2 种基金National Health Baby Promotion Program (No. FP2000NO13)Education Ministry Key Program (No. 02185)National Yangzi Scholar Program, 211 and 985 Projects of Peking University (No. 20020903)
文摘Objective To study the prevalence of different types of neural tube defects （NTDs） in Luliang Prefecture, Shanxi province, where the prevalence of NTDs is unusually high and the correlation between NTDs prevalence and patterns. Methods A surveillance population-based birth defects was performed in Luliang Prefecture, Shanxi province. Results The results of our study showed that the prevalence of NTDs was 2-fold higher in Luliang Prefecture than in other areas of Shanxi province. Unusual patterns of NTDs were found, however, multiple NTDs were relatively common in Luliang Prefecture, accounting for over 13% of all NTDs cases in China. Conclusion The prevalence of NTDs is associated with its patterns.
基金supported by the Science and Technology Key Program of Sichuan Provincial Health Ministry,No.080128
文摘In the field of developmental neurobiology, accurate and ordered regulation of the cell cycle and apoptosis are crucial factors contributing to the normal formation of the neural tube. Preliminary studies identified several genes involved in the development of neural tube defects. In this study, we established a model of developmental neural tube defects by administration of retinoic acid to pregnant rats. Gene chip hybridization analysis showed that genes related to the cell cycle and apoptosis, signal transduction, transcription and translation regulation, energy and metabolism, heat shock, and matrix and cytoskeletal proteins were all involved in the formation of developmental neural tube defects. Among these, cell cycle-related genes were predominant. Retinoic acid treat-ment caused differential expression of three cell cycle-related genes p57kip2, Cdk5 and Spin, the expression levels of which were downregulated by retinoic acid and upregulated during normal neural tube formation. The results of this study indicate that cell cycle-related genes play an im-portant role in the formation of neural tube defects. P57kip2, Cdk5 and Spin may be critical genes in the pathogenesis of neural tube defects.
基金Project supported by the National Natural Science Foundation of China (Nos. 40471111 and 70571076)the Ministry of Science and Technology of China (No. 2001CB5103)
文摘Objective: To estimate the prevalence rates of neural tube defects (NTDs) in Heshun County, Shanxi Province, China by Bayesian smoothing technique. Methods: A total of 80 infants in the study area who were diagnosed with NTDs were analyzed. Two mapping techniques were then used. Firstly, the GIS software ArcGIS was used to map the crude prevalence rates. Secondly, the data were smoothed by the method of empirical Bayes estimation. Results: The classical statistical approach produced an extremely dishomogeneous map, while the Bayesian map was much smoother and more interpretable. The maps produced by the Bayesian technique indicate the tendency of villages in the southeastern region to produce higher prevalence or risk values. Conclusions: The Bayesian smoothing technique addresses the issue of heterogeneity in the population at risk and it is therefore recommended for use in explorative mapping of birth defects. This approach provides procedures to identify spatial health risk levels and assists in generating hypothesis that will be investigated in further detail.
基金ThisworkwassupportedbytheNationalScienceFundforDistin guishedYoungScholarsfromtheNaturalScienceFoundationofChi na (No .30 12 5 0 19) ,andtheClinicalKeySubjectsfromtheMin istryofHealthofChina (No .970 2 4 0 )
文摘To evaluate the implication of methymalonic acid (MMA) in the early diagnosis of neural tube defects (NTD), a quantitative assay for MMA was established by using gas chromatography-mass spectrometry with stable isotope of MMA as an internal standard. Amniotic fluid and maternal urine MMA concentration, maternal serum folate, red blood cell folate and vitamin B 12 levels were measured in the middle term of NTD-affected and normal pregnancies. Amniotic fluid and maternal urine MMA concentrations in the middle term of NTD affected pregnancies (1.4±0.9 μmol/L, and 22.1±12.6 nmol/μmol creatinine) were significantly higher than that of normal pregnancies (1.0±0.4μmol/L, and 2.5±1.1 nmol/μmol creatinine). There was no significant difference between normal and NTD pregnancies for serum folate, red blood cell folate and vitamin B 12 levels. The results suggested that MMAs in amniotic fluid and maternal urine are sensitive markers for early diagnosis of NTD. Vitamin B 12 is an active cofactor involved in the remethylation of homocycteine and its deficiency is an independent risk factor for NTD. MMA is a specific and sensitive marker for intracellular vitamin B 12 deficiency. This study suggests that it is necessary to monitor the vitamin B 12 deficiency and advocates vitamin B 12 supplementation with folate prevention program.
基金sponsored by the National Natural Science Foundation of China, No. 31140012, 31040056,31140079the Natural Science Foundation of Shanxi Province,No. 2006011113
文摘The present study involved a questionnaire survey of 156 mothers that gave birth to children with neural tube defects or had a history of pregnancy resulting in children with neural tube defects （case group） and 156 control mothers with concurrent healthy children （control group） as well as detection of mitochondrial membrane transporter protein gene [uncoupling protein 2 （UCP2）] polymorphism. The maternal UCP2 3＇ untranslated region （UTR） D/D genotype and D allele frequency were significantly higher in the case group compared with the control group （odds ratio （OR） 3.233; 95% confidence interval （C/） 1.103 9.476; P= 0.040; OR： 3.484; 95% CI： for neural tube defects 2.109 5.753; P 〈 0.001）. Univariate and multivariate logistic regression analysis of risk factors for neural tube defects showed that a matemal UCP2 3＇ UTR D/D genotype was negatively interacted with the mothers＇ consumption of frequent fresh fruit and vegetables （S = 0.007）, positively interacted with the mothers＇ frequency of germinated potato consumption （S = 2.15） and positively interacted with the mothers＇ body mass index （S = 3.50）. These findings suggest that maternal UCP2 3＇ UTR gene polymorphism, pregnancy time, consumption of germinated potatoes and body mass index are associated with an increased risk for neural tube defects in children from mothers living in Shanxi province, China. Moreover, there is an apparent gene-environment interaction involved in the development of neural tube defects in offspring.
基金the National Key Project of Scientific and Technical Supporting Pro-grams funded by the Ministry of Science & Technology of China, No. 2007BA107A02the National Basic Research Program of China (973 Program), No. 2007CB511902+1 种基金Shanxi Scholarship Council of China, No. 2008-48the Natural Science Foundation of Shanxi Province, No. 2010011049-2
文摘Several studies have demonstrated that Slug,which encodes a zinc finger of the Snail family of transcription factors,is a potential risk factor for neural tube defects.Neural tube defects tend to occur with a high rate in Shanxi province,China.The present case-control study investigated genotypic distributions and allele frequencies of Slug C1548A polymorphisms in DNA samples from59 women with a history of neural tube defect pregnancies and 73 controls during the same period from Shanxi Province,China.Results demonstrated that women with a history of neural tube defect pregnancies had significantly greater genotypic distributions of Slug AA genotypes and A allele frequencies compared with controls,and A allele Slug C1548A was a risk factor for neural tube defects（odds ratio = 3.444;95% confidence interval;2.021-5.868,P 〈 0.05）.Three-dimensional structure prediction revealed that Slug C1548A resulted in transition of aspartic acid into glutamate at position 119.This indicated that these mutations could lead to damaged protein structure and function.These findings suggest that Slug C1548A gene polymorphism is closely related to neural tube defects in a population of Han Chinese origin from Shanxi Province,China
基金Supported by:the Scientific and Technological Foundation of Sichuan Public Health Bureau in 2008.No. 080128
文摘BACKGROUND： Neural tube defects can be induced by abnormal factors in vivo or in vitro during development. However, the molecular mechanisms of neural tube defect induction, and the related gene expression and regulation are still unknown. OBJECTIVE： To compare the differences in gene expression between normal embryos and those with neural tube defects. DESIGN, TIME AND SETTING： A neural development study was performed at the Department of Neurobiology, Third Military Medical University of Chinese PLA between January 2006 and October 2007. MATERIALS： Among 120 adult Kunming mice, 60 pregnant mice were randomly and evenly divided into a retinoic acid group （n = 30） and a normal control group （n =30）. The retinoic acid was produced by Sigma, USA, the gene microarray by the Amersham Pharmacia Company, Hong Kong, and the gene sequence was provided by the Incyte database, USA. METHODS： Retinoic acid was administered to prepare models of neural tube defects, and corn oil was similarly administered to the normal control group. Total RNA was extracted from embryonic tissue of the two groups using a Trizol kit, and a cDNA microarray containing 1 100 known genes was used to compare differences in gene expression between the normal control group and the retinoic acid group on embryonic （E） day 10.5 and 11.5. Several differentially expressed genes were randomly selected from the two groups for Northern blotting, to verify the results of the cDNA microarray. MAIN OUTCOME MEASURES： Morphological changes and differential gene expression between the normal control group and the retinoic acid group. RESULTS： Anatomical microscopy demonstrated that an intact closure of the brain was formed in the normal mouse embryos by days E10.5 and E11.5. The cerebral appearance was full and smooth, and the surface of the spine was intact. However, in the retinoic acid group on days E10.5 and E11.5, there were more dead embryos. Morphological malformations typically included non-closure at the top of the cranium and abnormal changes of the metencephalon and face. cDNA microarray analysis suggested that the changes in expression of seven different genes were similar on both days E10.5 and E11.5. These were downregulation of NekT, Igfbp5, Zw10, Csf3r, Psmc6 and Rb 1, and upregulation of Apoa-4. This study also indicated that Cdk5 expression was downregulated in the retinoic acid group on day E11.5. The results of the cDNA microarray analysis were partly confirmed by Northern blotting. CONCLUSION： Cdk5, Nek7, Igfbp5, Zw10, Csf3r, Psmc6, Rb1 and Apoa-4 may be key factors in retinoic acid-induced neural tube defects.
文摘<b><span style="font-family:;" "="">Background:</span></b><span style="font-family:;" "=""> As C677T mutation, A1298C mutation in methylene tetrahydrofolate reductase (MTHFR) gene results in a decreased MTHFR activity but </span><span style="font-family:;" "="">to</span><span style="font-family:;" "=""> a less extent, it is known as a risk factor of predisposition to human neural tube defects (NTDs), in some populations. Our objective was therefore to study, for the first time in Algerian population, if A1298C polymorphism confer</span><span style="font-family:;" "="">s </span><span style="font-family:;" "="">risk for the occurrence of this abnormality. We have examined the distribution of the genotype and the allele frequencies of A1298C mutation, and also their influence on plasma homocysteine (Hcy) concentration. <b>Patients and Methods:</b> We studied this polymorphism in 38 mothers of NTD cases and 67 control individuals of an eastern Algerian population. The muta<span>tion was determined by polymerase chain reaction</span></span><span style="font-family:;" "="">-</span><span style="font-family:;" "="">restriction fragm</span><span style="font-family:;" "="">ent length polymorphism analysis (PCR/RFLP). Plasma homocysteine concentration was analyzed using an automated chemiluminescence method. <b>Results:</b> No signi?cant association could be observed between allele and genotypes frequencies of A1298C MTHFR gene polymorphism and NTDs risk. However, we could observe that A1298C polymorphism affects homocysteine metabolism in mothers of NTD cases leading to homocysteine concentration values higher in AA genotype and lower in AC/CC genotypes (15.29</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">±</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">11.8 μmol/l <span>vs.<i> </i></span>8.63</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">±</span><span style="font-family:;" "=""> </span><span style="font-family:;" "="">3.83 μmol/l, <i>p</i> < 0.05). <b>Conclusion:</b> Data indicate that A1298C MTHFR gene polymorphism might be a risk factor by affecting homocysteine metabolism in mothers of Algerian children with NTDs.</span>
基金supported by National Natural Science Foundation of China(No.41101431)the fourth installment special funding of China Postdoctoral Science Foundation(No.201104003)+1 种基金China Postdoctoral Science Foundation(No.20100470004)the State Key Funds of Social Science Project(Research on Disability Prevention Measurement in China,No.09&ZD072)
文摘Abstract Objective To develop a new technique for assessing the risk of birth defects, which are a major cause of infant mortality and disability in many parts of the world. Methods The region of interest in this study was Heshun County, the county in China with the highest rate of neural tube defects （NTDs）. A hybrid particle swarm optimization/ant colony optimization （PSO/ACO） algorithm was used to quantify the probability of NTDs occurring at villages with no births. The hybrid PSO/ACO algorithm is a form of artificial intelligence adapted for hierarchical classification. It is a powerful technique for modeling complex problems involving impacts of causes. Results The algorithm was easy to apply, with the accuracy of the results being 69.5%＋7.02% at the 95% confidence level. Conclusion The proposed method is simple to apply, has acceptable fault tolerance, and greatly enhances the accuracy of calculations.
基金This research was supported by the grants from the National Natural Science Foundation of China （No. 31140012, and No. 31040056） the Natural Science Foundation of Shanxi Province （No. 200611113） and Shanxi Scholarship Council of China （No. 2010-52）.
文摘Background The 5,10-methylenetetrahydrofolate reductase （MTHFR） and methionine synthase （MS） are attractive candidates for screening for risk of neural tube defects （NTDs）. The aim of the current study was to investigate maternal MTHFR and MS polymorphisms and the interaction between them and their influence on children with NTDs in the Shanxi Province of northern China. Methods Fifty-one mothers who previously had children with NTDs constituted the case group and 51 age-matched mothers with children that were unaffected by any birth defects constituted the control group. All subjects were genotyped for MTHFR C677T and MS A2756G polymorphisms. SPSS 11.5 software package was used for all analyses. Results There was a significant difference for MTHFR genotype distribution for one site （C677T） between the case and control groups. The T allele frequencies were significantly higher in the case group than in the control group （55.9% vs. 35.3%, P 〈0.05）. A lack of association was observed for the MS A2756G polymorphism. There was an interaction between the maternal MTHFR C677T genotype and MS A2756G genotype. Conclusion Genetic interaction between MTHFR and MS genes raises the probability of neural tube defects.
文摘Background Maternal exposure to nitrate, nitrite, and N-nitroso compounds from drinking water or diet has been associated with an increased risk of neural tube defects （NTDs） in some studies. Pickled vegetables contain relatively large amounts of nitrite and N-nitroso compounds. We examined the association between maternal periconceptional consumption of pickled vegetables and NTDs in Shanxi Province of northern China. Methods Data were derived from a population based case-control study of major external birth defects in four counties of $hanxi Province. Participants included 519 NTDs cases identified between 2003 and 2007 and 694 healthy controls. Exposure information was collected within 1 week after delivery. Multivariable non-conditioanal Logistic regression model was used to estimate the adjusted odds ratio （OR） controlling for potential confounding variables.
基金This study was supported by the National Key Project of Scientific and Technical Supporting Programs funded by the Ministry of Science ＆ Technology of China （No. 2007BA107A02）, the National Basic Research Program of China （973 Program, No.2007CB511902）, Shanxi Scholarship Council of China （No.2008-48）, Major Program of Shanxi Natural Science Foundation of China （No. 2010011049-2） and the National Key Project of Scientific and Technical Supporting Programs funded by the Ministry of Science ＆ Technology of China （No. 31040056）.
文摘Background Neural tube defects are the most common human birth defects. The causes are multifactorial with complex genetic and environmental factors, although the exact genetic causes are unknown. This research was conducted to study the frequency of Msx2 gene polymorphisms in 59 women with a history of pregnancy with a neural tube defect and in 73 healthy controls. We aimed to determine the effect of this genetic polymorphism on the incidence of neural tube defects in the Han Chinese population.Methods We studied 59 mothers with at least one previous child with a neural tube defect （the case group） and 73case-control subjects during the same period, from Shanxi Province, China. We analyzed the genotypic distributions and allele frequencies of Msx2 C386T poiymorphisms in DNA samples from the case and control groups. A three-dimensional protein model was predicted using Swiss-Pdb Viewer software version 4.0. Disease association was analyzed using chi-square tests.Results Significant differences were observed in the genotypes and allele frequencies of the Msx2 C386T allele between the case and control groups （CT： 32% vs. 15%, P=0.0073 and TT 15% vs. 4%, P=0.013, respectively）. Logistic regression analysis showed that the C386T mutation is a potential risk factor for neural tube defects （P 〈0.05; OR： 3.466;95%CI： 1.831-6.560）. Three-dimensional structure prediction revealed that the Msx2 C386T mutation results in a threonine substitution for methionine at position 129 of exon 2, which might lead to structural mutations or dysfunctions in the protein encoded by Msx2.Conclusion Maternal Msx2 C386T gene polymorphisms were associated with fetal neural tube defects in Han Chinese women in Shanxi Province.
基金supported by the Development and Innovation Foundation of Jinan University,Guangdong Province,China(21611613)the National Natural Science Foundation of China(81271280)
文摘The protein composition of cerebrospinal fluid（CSF） in neural tube defects（NTDs） remains unknown. We investigated the protein composition of CSF from 9 infants with NTDs using isobaric tags for relative and absolute quantitation（iTRAQ）. We identified 568 proteins in the CSF of infants with spina bifida, which is the most common type of NTD. Among these, 18 proteins were associated with neural tube closure in the CSF during human embryonic neurulation and 5 were involved in NTDs. Based on these results, an animal model was further utilized to investigate early serum biomarkers for NTDs.We found that the myristoylated alanine-rich C-kinase substrate, Kunitz-type protease inhibitor 2, andapolipoprotein B-100 protein levels were decreased in both embryos and the sera of pregnant Sprague-Dawley rats carrying embryos with NTDs. CSF proteins may be useful in the discovery of potential serum biomarkers for NTDs.
文摘Neural tube defects （NTDs） are a group of birth anomalies having a profound physical, emotional, and financial effects on families and communities. Their etiology is complex, involving environmental and genetic factors that interact to modulate the incidence and severity of the developing phenotype. The planar cell polarity （PCP） pathway controls the process of convergent extension （CE） during gastrulation and neural tube closure and has been implicated in the pathogenesis of NTDs in animal models and human cohorts. This review summarizes the cumulative results of recent studies on PCP signaling pathway and human NTDs. These results demonstrate that PCP gene alterations contribute to the etiology of human NTDs.
基金Scientific and Technological Projects of Sichuan Provincial Health Department, No. 080128
文摘To date, little information has been available regarding genes involved in the regulation of embryonic cell development, which participate in retinoic acid-induced neural tube defects in mice. Previous studies have revealed seven differentially expressed genes involved in neural tube developmental defects. However, gene expression and regulation is a complex process. Therefore, gene expression differences between normal and defective neural tubes at 9.5 and 10.5 days were compared. A total of eight differentially expressed genes exhibited coincident alterations at embryonic 9.5 and 10.5 days. In mice with retinoic acid-induced neural tube defects, NeK7, IGFBP5 ZW10, Csf3r, PSMC6, Cdk5, and Rbl expressions were downregulated, but Apoa-4 expression was upregulated. These results were confirmed by Northern blot hybridization. Results suggested that NeK7, IGFBP5, ZW10, Csf3r, PSMC6, Cdk5, Rb1, and Apoa-4 are important regulatory factors involved in neural tube defects.
基金This work was supported by grants from the National Key Basic Research Program of China[2016YFC1000502 to H.Wang and X Yang]the National Natural Science Foundation of China[81430005 to H Wang,81472050 to X Yang]Open project of National Population and Family Planning Key Laboratory of Contraceptive drugs and Devices[2016KF04 for X Yang].
文摘Background:The sonic hedgehog(SHH)pathway is an important signaling pathway for neural tube closure.GLI family zinc finger 2(GLI2)is the major activation mediator of the SHH pathway;however,no single-nucleotide polymorphisms(SNPs)in GLI2 have been reported to be associated with human neural tube defects(NTDs)to date.Here,we evaluated a mutation in GLI2 in the Han Chinese population.Methods:We used SNPscan to genotype rs3738880 in the GLI2 coding region.We then investigated the function of this gene by Western blotting and dual-luciferase assays.Results:In this study,we found that the GLI2 missense variant rs3738880 significantly increased the risk of NTDs in the Han Chinese population via association studies in a cohort of 254 patients and 277 controls from Shanxi Province(odds ratio[OR]=1.89,95%confidence interval[CI]=1.28-2.80,P=0.0012).Additional stratified analyses demonstrated that rs3738880 was significantly related to spina bifida(114 cases,OR=2.01,95%CI=1.19–3.38,P=0.0067).Functional analysis revealed that rs3738880 did not affect GLI2 protein stability and significantly increased SHH activity because of the introduction of a potential phosphorylation site in GLI2.Conclusion:rs3738880 was a risk factor for NTDs in the Han Chinese population.
基金supported by grants from the National Natural Science Foundation of China (30425011 30530380)the Innovation Project of the Chinese Academy of Sciences (KSCX2-YW-R-090)~~
文摘Neural tube defects （NTDs） are severe congenital malformation diseases, which occur in 1 out of 1000 births in human. In Xenopus, several tissue movements are involved in the neural tube closure process. Immediately after the neural tube fusion, the neural crest cells get monopolar protrusion toward dorsal midline and migrate to form the roof of the neural tube. At the same time, radial intercalation takes place from the ventral neural tube and forces it to be single-layered. Here, we physically block the neural tube closure to test the cell movements and the following patterning in Xenopus laevis explants. The results show that the single-layered neural tube fails to form and the neural crest cells remain at the lateral regions in the explants with NTDs. However, the patterning of the neural tube is not affected as indicated by the normal expression of the preneural genes. These results indicate a requirement of the neural tube fusion for the radial intercalation and the dorsal midline directed neural crest migration, but not for the dorsal-ventral patterning of the neural tube.
