Transcriptomic profile analysis of mouse neural tube development by RNA‐Seq

Yu, Jianhua; Mu, Jianbing; Guo, Qin; Yang, Lihong; Zhang, Juan; Liu, Zhizhen; Yu, Bin; Zhang, Ting; Xie, Jun

doi:10.1002/iub.1653

Cited by 25 publications

(19 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The NTDs mouse models used was the same as described previously in our laboratory 20,21 . Mouse nervous system development starts on day 7.5 and get completed on day 10.5 of embryonic development 22,23 Keeping this in view, neural tissues were examined on day E9.5, because at this time point the nervous development is still in progress. The intact morphology of normal mouse embryos and the morphology of NTDs mouse embryos on day E9.5 were shown in Fig.…”

Section: Gcm1 and Wnt Target Genes Upregulation In Ntdsmentioning

confidence: 99%

Aberrant Gcm1 expression mediates Wnt/β-catenin pathway activation in folate deficiency involved in neural tube defects

Xie

Gao

et al. 2021

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

Wnt signaling plays a major role in early neural development. An aberrant activation in Wnt/β-catenin pathway causes defective anteroposterior patterning, which results in neural tube closure defects (NTDs). Changes in folate metabolism may participate in early embryo fate determination. We have identified that folate deficiency activated Wnt/β-catenin pathway by upregulating a chorion-specific transcription factor Gcm1. Specifically, folate deficiency promoted formation of the Gcm1/β-catenin/T-cell factor (TCF4) complex formation to regulate the Wnt targeted gene transactivation through Wnt-responsive elements. Moreover, the transcription factor Nanog upregulated Gcm1 transcription in mESCs under folate deficiency. Lastly, in NTDs mouse models and low-folate NTDs human brain samples, Gcm1 and Wnt/β-catenin targeted genes related to neural tube closure are specifically overexpressed. These results indicated that low-folate level promoted Wnt/β-catenin signaling via activating Gcm1, and thus leaded into aberrant vertebrate neural development.

show abstract

Section: Gcm1 and Wnt Target Genes Upregulation In Ntdsmentioning

confidence: 99%

Aberrant Gcm1 expression mediates Wnt/β-catenin pathway activation in folate deficiency involved in neural tube defects

Xie

Gao

et al. 2021

Cell Death Dis

Self Cite

View full text Add to dashboard Cite

show abstract

“…Transcriptional profiling by microarray has been an important tool in elucidating the molecular pathways controlling this process for over a decade, and massively parallel sequencing has been used more recently in this regard [ 20 , 21 ]. In this work, we used transcriptomic profiling by RNA-Seq to gain insights on underlying molecular determinants of NTD in mouse embryos lacking the HDL receptor SR-B1.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional profiling of embryos lacking the lipoprotein receptor SR-B1 reveals a regulatory circuit governing a neurodevelopmental or metabolic decision during neural tube closure

et al. 2018

View full text Add to dashboard Cite

BackgroundThe high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, including cholesterol and vitamin E. During early mouse development, SR-B1 is located in the maternal-fetal interface, where it facilitates vitamin E transport towards the embryo. Consequently, mouse embryos lacking SR-B1 are vitamin E-deficient, and around half of them fail to close the neural tube and show cephalic neural tube defects (NTD). Here, we used transcriptomic profiling to identify the molecular determinants of this phenotypic difference between SR-B1 deficient embryos with normal morphology or with NTD.ResultsWe used RNA-Seq to compare the transcriptomic profile of three groups of embryos retrieved from SR-B1 heterozygous intercrosses: wild-type E9.5 embryos (WT), embryos lacking SR-B1 that are morphologically normal, without NTD (KO-N) and SR-B1 deficient embryos with this defect (KO-NTD). We identified over 1000 differentially expressed genes: down-regulated genes in KO-NTD embryos were enriched for functions associated to neural development, while up-regulated genes in KO-NTD embryos were enriched for functions related to lipid metabolism. Feeding pregnant dams a vitamin E-enriched diet, which prevents NTD in SR-B1 KO embryos, resulted in mRNA levels for those differentially expressed genes that were more similar to KO-N than to KO-NTD embryos. We used gene regulatory network analysis to identify putative transcriptional regulators driving the different embryonic expression profiles, and identified a regulatory circuit controlled by the androgen receptor that may contribute to this dichotomous expression profile in SR-B1 embryos. Supporting this possibility, the expression level of the androgen receptor correlated strongly with the expression of several genes involved in neural development and lipid metabolism.ConclusionsOur analysis shows that normal and defective embryos lacking SR-B1 have divergent expression profiles, explained by a defined set of transcription factors that may explain their divergent phenotype. We propose that distinct expression profiles may be relevant during early development to support embryonic nutrition and neural tube closure.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-5110-2) contains supplementary material, which is available to authorized users.

show abstract

“…After the step-down test, mice were euthanized by cervical dislocation, and their brain samples were collected respectively (13).…”

Section: Step-down Testmentioning

confidence: 99%

Identify the regulatory network of LncRNA HAR1A in neurological development by RNA-Sequencing and bioinformatics analysis.

Zhang

Lin

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: LncRNA HAR1A, which is explicitly expressed in Cajal-Retzius neurons (CRs), has been reported to be related to the development of the human brain. As one of the human accelerated regions (HARs) gene, it plays an important role in central neural evolution. Dysregulation of lncRNA HAR1A was associated with many central nervous system diseases. Methods:We cloned human gene HAR1A into the EF-1α promoter vector to make the transgenic mice. To observe the changes in memory and cognitive ability of mice, we conducted the Morris water maze (MWM) test and step-down passive avoidance test. RNA-seq analysis was performed to identify the differentially expressed genes (DEGs) of the experiment and control group. Systematic bioinformatic analysis was used to confirm the pathway and function that the DEGs enriched in. 523 human gene expression datasets were downloaded from The Cancer Genome Atlas (TCGA) for Co-expression analysis. Through Co-expression analysis, we obtained the Protein-Protein Interactions Network (PPI-Net) and enrichment pathways of LncRNA HAR1A's co-expression genes in human. Results:The memory and cognitive ability of the transgene mice were significantly improved. Results of GO analysis showed that cerebral cortex development is the most significant function related to HAR1A in brain development. DEGs enriched in this function included Lhx2, Emx2, Foxg1, Nr2e1, Emx1. They all play an important role in the regulation of CRs' function. "Cellular response to calcium ion" exhibited the highest rich factor in the Gene Ontology (GO) analysis. Core genes in the PPI-Net were SNAP25, GRIN1, SYN1, DLG4, CAMK2A. SNAP25, SYN1 relate to synaptic function. GRIN1, DLG4 and CAMK2A relate to synapse formation. GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs and HAR1A 's Co-expressed genes in 523 human gene expression datasets show that synapse, axon guidance, synaptic signaling and ligand-receptor interaction are significant.Conclusions:Overexpress HAR1A will improve the memory and cognitive ability of the transgene mice. The possible mechanism is HAR1A affects brain development by regulating CRs' function. Moreover, HAR1A may be involved in ligand-receptor interaction, Axon guidance and synapse formation, which are important for brain development and evolution. Cellular response to calcium may play an important role in those process.

show abstract

Transcriptomic profile analysis of mouse neural tube development by RNA‐Seq

Cited by 25 publications

References 71 publications

Aberrant Gcm1 expression mediates Wnt/β-catenin pathway activation in folate deficiency involved in neural tube defects

Aberrant Gcm1 expression mediates Wnt/β-catenin pathway activation in folate deficiency involved in neural tube defects

Transcriptional profiling of embryos lacking the lipoprotein receptor SR-B1 reveals a regulatory circuit governing a neurodevelopmental or metabolic decision during neural tube closure

Identify the regulatory network of LncRNA HAR1A in neurological development by RNA-Sequencing and bioinformatics analysis.

Contact Info

Product

Resources

About