scholarly journals Molecular regulation of fetal brain development in pigs

2021 ◽  
Author(s):  
◽  
Monica P. Strawn
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factor ◽  
Brain Development ◽  
Early Development ◽  
Expression Patterns ◽  
Fetal Brain ◽  
Molecular Regulation ◽  
Fetal Brain Development ◽  
The Brain

Two experiments were conducted to investigate molecular regulation that impacts fetal brain development in pigs. In the first experiment (Chapter 2), gene expression was profiled by RNA sequencing (RNA-seq) to examine the whole transcriptome of the male (M) and female (F) fetal brain at gestation day (d) 45, 60 and 90. The analysis showed fewer differentially expressed genes (DEGs) in the brain of male and female fetuses in earlier gestation (d45-d60) when compared to late gestation (d60-d90). The homeobox (HOX) A5 gene that regulates pattern formation in early development was in the top upregulated DEGs between d45 to d60 in fetuses of both sexes. This study also found HOX B5 and D3 genes were in the top upregulated genes between d45 and d60 of the fetal brain of females, but not males. The second experiment (Chapter 3) investigated DNA methylation in pigs. DNA methylation in the fetal brain of both sexes at the same three gestation days was performed by enzymatic methyl sequencing (EM-seq). Hotspots of methylation in specific chromosomal regions were observed in the analysis. The analysis identified 1,475 sites in the pig genome that were methylated in the fetal brain, irrespective of sex, during development. The same sites were methylated in a canonically correlated manner in the blood of the adult stage, both in sows and boars. This is consistent with the Dilman theory of developmental aging (DevAge), which suggests that aging and early development of the brain are regulated by common molecular processes. A comparative analysis (Chapter 4) compared the gene expression patterns in the fetal brain and placenta between pigs and mice. The analysis identified 112 genes that were expressed (mean FPKM > 10) in the fetal brain of both species but not expressed (mean FPKM < 1) in the placenta of either species, and 10 genes that were expressed in the placenta of both species but not expressed in the fetal brain. In-silico analysis of the transcription factor binding sites in the 500 bp of the upstream DNA of these common genes revealed that they were commonly regulated by the RE1 silencing transcription factor (REST), which is a multifaceted transcription factor that acts as a master regulator of neurogenesis as well as controls neural excitation and the aging processes.

scholarly journals Gene expression levels of DNA methyltransferase enzymes in Shank3-deficient mouse model of autism during early development

2021 ◽  
Vol 55 (4) ◽  
pp. 234-237
Author(s):  
Annamaria Srancikova ◽  
Alexandra Reichova ◽  
Zuzana Bacova ◽  
Jan Bakos
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Brain Development ◽  
Early Development ◽  
Molecular Mechanisms ◽  
Altered Expression ◽  
Expression Levels ◽  
The Brain ◽  
Deficient Mice ◽  
Gene Expression Levels

Abstract Objectives. The balance between DNA methylation and demethylation is crucial for the brain development. Therefore, alterations in the expression of enzymes controlling DNA methylation patterns may contribute to the etiology of neurodevelopmental disorders, including autism. SH3 and multiple ankyrin repeat domains 3 (Shank3)-deficient mice are commonly used as a well-characterized transgenic model to investigate the molecular mechanisms of autistic symptoms. DNA methyltransferases (DNMTs), which modulate several cellular processes in neurodevelopment, are implicated in the pathophysiology of autism. In this study, we aimed to describe the gene expression changes of major Dnmts in the brain of Shank3-deficient mice during early development. Methods and Results. The Dnmts gene expression was analyzed by qPCR in 5-day-old homo-zygous Shank3-deficient mice. We found significantly lower Dnmt1 and Dnmt3b gene expression levels in the frontal cortex. However, no such changes were observed in the hippocampus. However, significant increase was observed in the expression of Dnmt3a and Dnmt3b genes in the hypothalamus of Shank3-deficient mice. Conclusions. The present data indicate that abnormalities in the Shank3 gene are accompanied by an altered expression of DNA methylation enzymes in the early brain development stages, therefore, specific epigenetic control mechanisms in autism-relevant models should be more extensively investigated.

scholarly journals Evidence in cortical folding patterns for prenatal predispositions to hallucinations in schizophrenia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Colleen P. E. Rollins ◽  
Jane R. Garrison ◽  
Maite Arribas ◽  
Aida Seyedsalehi ◽  
Zhi Li ◽  
...  
Keyword(s):  
Brain Development ◽  
Large Scale ◽  
Fetal Brain ◽  
Brain Structures ◽  
Physical Reality ◽  
Healthy Controls ◽  
Cortical Folding ◽  
Diverse World ◽  
Fetal Brain Development ◽  
The Brain

Abstract All perception is a construction of the brain from sensory input. Our first perceptions begin during gestation, making fetal brain development fundamental to how we experience a diverse world. Hallucinations are percepts without origin in physical reality that occur in health and disease. Despite longstanding research on the brain structures supporting hallucinations and on perinatal contributions to the pathophysiology of schizophrenia, what links these two distinct lines of research remains unclear. Sulcal patterns derived from structural magnetic resonance (MR) images can provide a proxy in adulthood for early brain development. We studied two independent datasets of patients with schizophrenia who underwent clinical assessment and 3T MR imaging from the United Kingdom and Shanghai, China (n = 181 combined) and 63 healthy controls from Shanghai. Participants were stratified into those with (n = 79 UK; n = 22 Shanghai) and without (n = 43 UK; n = 37 Shanghai) hallucinations from the PANSS P3 scores for hallucinatory behaviour. We quantified the length, depth, and asymmetry indices of the paracingulate and superior temporal sulci (PCS, STS), which have previously been associated with hallucinations in schizophrenia, and constructed cortical folding covariance matrices organized by large-scale functional networks. In both ethnic groups, we demonstrated a significantly shorter left PCS in patients with hallucinations compared to those without, and to healthy controls. Reduced PCS length and STS depth corresponded to focal deviations in their geometry and to significantly increased covariance within and between areas of the salience and auditory networks. The discovery of neurodevelopmental alterations contributing to hallucinations establishes testable models for these enigmatic, sometimes highly distressing, perceptions and provides mechanistic insight into the pathological consequences of prenatal origins.

scholarly journals Altered Hippocampal Gene Expression and Morphology in Fetal Piglets following Maternal Respiratory Viral Infection

2018 ◽  
Vol 40 (2) ◽  
pp. 104-119 ◽  
Author(s):  
Adrienne M. Antonson ◽  
Bindu Balakrishnan ◽  
Emily C. Radlowski ◽  
Geraldine Petr ◽  
Rodney W. Johnson
Keyword(s):  
Gene Expression ◽  
Viral Infection ◽  
Brain Development ◽  
Hippocampal Neurons ◽  
Protein A ◽  
Fetal Brain ◽  
Respiratory Syndrome Virus ◽  
Maternal Infection ◽  
Ki 67 ◽  
Fetal Brain Development

Maternal infection during pregnancy increases the risk of neurobehavioral problems in offspring. Evidence from rodent models indicates that the maternal immune response to infection can alter fetal brain development, particularly in the hippocampus. However, information on the effects of maternal viral infection on fetal brain development in gyrencephalic species is limited. Thus, the objective of this study was to assess several effects of maternal viral infection in the last one-third of gestation on hippocampal gene expression and development in fetal piglets. Pregnant gilts were inoculated with porcine reproductive and respiratory syndrome virus (PRRSV) at gestational day (GD) 76 and the fetuses were removed by cesarean section at GD 111 (3 days before anticipated parturition). The gilts infected with PRRSV had elevated plasma interleukin-6 levels and developed transient febrile and anorectic responses lasting approximately 21 days. Despite having a similar overall body weight, fetuses from the PRRSV-infected gilts had a decreased brain weight and altered hippocampal gene expression compared to fetuses from control gilts. Notably, maternal infection caused a reduction in estimated neuronal numbers in the fetal dentate gyrus and subiculum. The number of proliferative Ki-67+ cells was not altered, but the relative integrated density of GFAP+ staining was increased, in addition to an increase in GFAP gene expression, indicating astrocyte-specific gliosis. Maternal viral infection caused an increase in fetal hippocampal gene expression of the inflammatory cytokines TNF-α and IFN-γ and the myelination marker myelin basic protein. MHCII protein, a classic monocyte activation marker, was reduced in microglia, while expression of the MHCII gene was decreased in hippocampal tissue of the fetuses from PRRSV-infected gilts. Together, these data suggest that maternal viral infection at the beginning of the last trimester results in a reduction in fetal hippocampal neurons that is evident 5 weeks after infection, when fetal piglets are near full term. The neuronal reduction was not accompanied by pronounced neuroinflammation at GD 111, indicating that any activation of classic neuroinflammatory pathways by maternal viral infection, if present, is mostly resolved by parturition.

ISDN2014_0171: Dynamic and sex‐specific changes in DNA methylation during human fetal brain development

2015 ◽  
Vol 47 (Part_A) ◽  
pp. 50-51
Author(s):  
H. Spiers ◽  
N.J. Bray ◽  
E. Hannon ◽  
L.C. Schalkwyk ◽  
C.C. Wong ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Brain Development ◽  
Fetal Brain ◽  
Human Fetal Brain ◽  
Fetal Brain Development

scholarly journals Functional analysis of enhancer elements regulating the expression of the Drosophila homeodomain transcription factor DRx by gene targeting

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Christine Klöppel ◽  
Kirsten Hildebrandt ◽  
Dieter Kolb ◽  
Nora Fürst ◽  
Isabelle Bley ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Brain Development ◽  
Gene Targeting ◽  
Developmental Stages ◽  
Expression Patterns ◽  
Adult Brain ◽  
Central Complex ◽  
Larval Brain ◽  
Endogenous Expression ◽  
The Brain

Abstract Background The Drosophila brain is an ideal model system to study stem cells, here called neuroblasts, and the generation of neural lineages. Many transcriptional activators are involved in formation of the brain during the development of Drosophila melanogaster. The transcription factor Drosophila Retinal homeobox (DRx), a member of the 57B homeobox gene cluster, is also one of these factors for brain development. Results In this study a detailed expression analysis of DRx in different developmental stages was conducted. We show that DRx is expressed in the embryonic brain in the protocerebrum, in the larval brain in the DM and DL lineages, the medulla and the lobula complex and in the central complex of the adult brain. We generated a DRx enhancer trap strain by gene targeting and reintegration of Gal4, which mimics the endogenous expression of DRx. With the help of eight existing enhancer-Gal4 strains and one made by our group, we mapped various enhancers necessary for the expression of DRx during all stages of brain development from the embryo to the adult. We made an analysis of some larger enhancer regions by gene targeting. Deletion of three of these enhancers showing the most prominent expression patterns in the brain resulted in specific temporal and spatial loss of DRx expression in defined brain structures. Conclusion Our data show that DRx is expressed in specific neuroblasts and defined neural lineages and suggest that DRx is another important factor for Drosophila brain development.

scholarly journals DNA Methylation and Expression Profiles of Whole Blood in Parkinson’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Adrienne R. Henderson ◽  
Qi Wang ◽  
Bessie Meechoovet ◽  
Ashley L. Siniard ◽  
Marcus Naymik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Parkinson’S Disease ◽  
Dna Methylation ◽  
Parkinson's Disease ◽  
Transcription Factor ◽  
Whole Blood ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Motor Deficits ◽  
Age Related

Parkinson’s disease (PD) is the second most common age-related neurodegenerative disease. It is presently only accurately diagnosed at an advanced stage by a series of motor deficits, which are predated by a litany of non-motor symptoms manifesting over years or decades. Aberrant epigenetic modifications exist across a range of diseases and are non-invasively detectable in blood as potential markers of disease. We performed comparative analyses of the methylome and transcriptome in blood from PD patients and matched controls. Our aim was to characterize DNA methylation and gene expression patterns in whole blood from PD patients as a foundational step toward the future goal of identifying molecular markers that could predict, accurately diagnose, or track the progression of PD. We found that differentially expressed genes (DEGs) were involved in the processes of transcription and mitochondrial function and that PD methylation profiles were readily distinguishable from healthy controls, even in whole-blood DNA samples. Differentially methylated regions (DMRs) were functionally varied, including near transcription factor nuclear transcription factor Y subunit alpha (NFYA), receptor tyrosine kinase DDR1, RING finger ubiquitin ligase (RNF5), acetyltransferase AGPAT1, and vault RNA VTRNA2-1. Expression quantitative trait methylation sites were found at long non-coding RNA PAX8-AS1 and transcription regulator ZFP57 among others. Functional epigenetic modules were highlighted by IL18R1, PTPRC, and ITGB2. We identified patterns of altered disease-specific DNA methylation and associated gene expression in whole blood. Our combined analyses extended what we learned from the DEG or DMR results alone. These studies provide a foundation to support the characterization of larger sample cohorts, with the goal of building a thorough, accurate, and non-invasive molecular PD biomarker.

scholarly journals Sexually Dimorphic Transcriptomic Changes of Developing Fetal Brain Reveal Signaling Pathways and Marker Genes of Brain Cells in Domestic Pigs

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2439
Author(s):  
Monica Strawn ◽  
Joao G. N. Moraes ◽  
Timothy J. Safranski ◽  
Susanta K. Behura
Keyword(s):  
Gene Expression ◽  
Brain Development ◽  
Signaling Pathways ◽  
Expression Patterns ◽  
Fetal Brain ◽  
Differentially Expressed ◽  
Marker Genes ◽  
Pathway Enrichment Analysis ◽  
Female Brain ◽  
Transcriptomic Changes

In this study, transcriptomic changes of the developing brain of pig fetuses of both sexes were investigated on gestation days (GD) 45, 60 and 90. Pig fetal brain grows rapidly around GD60. Consequently, gene expression of the fetal brain was distinctly different on GD90 compared to that of GD45 and GD60. In addition, varying numbers of differentially expressed genes (DEGs) were identified in the male brain compared to the female brain during development. The sex of adjacent fetuses also influenced gene expression of the fetal brain. Extensive changes in gene expression at the exon-level were observed during brain development. Pathway enrichment analysis showed that the ionotropic glutamate receptor pathway and p53 pathway were enriched in the female brain, whereas specific receptor-mediated signaling pathways were enriched in the male brain. Marker genes of neurons and astrocytes were significantly differentially expressed between male and female brains during development. Furthermore, comparative analysis of gene expression patterns between fetal brain and placenta suggested that genes related to ion transportation may play a key role in the regulation of the brain-placental axis in pig. Collectively, the study suggests potential application of pig models to better understand influence of fetal sex on brain development.

scholarly journals Response of wheat DREB transcription factor to drought stress based on DNA methylation

2021 ◽  
Author(s):  
Yanqiu Zhu ◽  
Huihui Wang ◽  
Wenjing Jia ◽  
Xiaoyan Wei ◽  
Zhikun Duan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factor ◽  
Drought Stress ◽  
Promoter Methylation ◽  
Expression Patterns ◽  
Dreb Transcription Factor ◽  
The Status ◽  
Element Binding Protein ◽  
Responsive Element

Abstract Background: The growth and development of wheat are seriously influenced by drought, dehydration responsive element binding protein (DREB) plays an important role in the response of plant to drought stress, but epigenetic regulation for gene expression of DREB transcription factor is less studied, especially the regulatory role of DNA methylation has not been reported.Results: In this research, DREB2, DREB6 and Wdreb2 were cloned from wheat AK58, and one 712-bp intron was identified in DREB6. Although AP2/EREBP domains of DREB2, DREB6 and Wdreb2 showed 73.25% identity, they belong to different types of DREB transcription factor. Under drought stress, different transcript expression patterns of DREB2, DREB6 and Wdreb2 were observed, and their expression had tissue specificity, was obviously higher in leaves. Promoters of DREB2, DREB6 and Wdreb2 were further studied, some elements related to stresses were found, and the promoters of DREB2 and Wdreb2 were slightly methylated, but DREB6 promoter was moderately methylated. Compared with the control, the level of promoter methylation in DREB2 and DREB6 decreased after 2 h stress treatment, and then increased, which was opposite in Wdreb2 promoter, the status of promoter methylation in DREB2, DREB6 and Wdreb2 also had significant changes under drought stress. Further analysis showed that promoter methylation of DREB6 and Wdreb2 was negatively correlated with their expression, especially in Wdreb2. Conclusions: Our data suggest the different functions of DREB2, DREB6 and Wdreb2 in response to drought stress, and demonstrate the strong effects of promoter methylation on the regulation of Wdreb2 and DREB6 gene expression.

Prenatal Origin of Hemiparetic Cerebral Palsy: How Often and Why?

PEDIATRICS ◽  
1991 ◽  
Vol 88 (5) ◽  
pp. 1059-1062
Author(s):  
KARIN B. NELSON
Keyword(s):  
Nervous System ◽  
Human Brain ◽  
Brain Development ◽  
Fetal Brain ◽  
New Information ◽  
Early Injury ◽  
Fetal Brain Development ◽  
Complicated Object ◽  
Infant Brain ◽  
The Brain

"Consider what must be accomplished during the course of fetal brain development. In effect, in a few months the entire work of hundreds of millions of years of evolution must be reachieved. . . . Tens of billions of neurons must be born. . . . These new cells must find their way to their anatomical destinations, sometimes moving over substantial distances in an embryo that is constantly changing in form. . . Once the cell is fixed in place, the axon must find its way to its own destination. . . . They must not only get where they are going and make a connection, but they must avoid making any number of other connections that they might wrongly make in places they pass. Each nerve cell must develop one or more of at least a dozen neurotransmitters. . . ." The product of that miracle is the most complicated object in the known universe, a human brain. In this "Decade of the Brain," we can anticipate the emergence of a great deal more information about how the nervous system develops, prenatally and thereafter, and how and when that development can go awry. That information will come from laboratories, clinics, and nurseries. Neuroimaging of the infant brain, a subject now producing a rich harvest in journals of pediatrics, neurology, radiology, and obstetrics, will contribute important new information about the processes of brain development in our species, the timing of derailment from the normal course of brain development, and some aspects of pathogenesis. Neuropathology and the enormous flowering of new approaches in the basic and clinical neurosciences will help in explication of the mechanisms of maldevelopment and early injury. And we can hope that identification of mechanisms will allow us to develop strategies to prevent at least some of the problems leading to prenatal damage of the developing human brain.

scholarly journals DNA Methylation Regulates Transcription Factor-Specific Neurodevelopmental but Not Sexually Dimorphic Gene Expression Dynamics in Zebra Finch Telencephalon

2021 ◽  
Vol 9 ◽  
Author(s):  
Jolien Diddens ◽  
Louis Coussement ◽  
Carolina Frankl-Vilches ◽  
Gaurav Majumdar ◽  
Sandra Steyaert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transcription Factor ◽  
Zebra Finch ◽  
Dosage Compensation ◽  
Expression Patterns ◽  
Song Learning ◽  
Sexually Dimorphic ◽  
Gene Expression Dynamics ◽  
Dimorphic Gene Expression

Song learning in zebra finches (Taeniopygia guttata) is a prototypical example of a complex learned behavior, yet knowledge of the underlying molecular processes is limited. Therefore, we characterized transcriptomic (RNA-sequencing) and epigenomic (RRBS, reduced representation bisulfite sequencing; immunofluorescence) dynamics in matched zebra finch telencephalon samples of both sexes from 1 day post hatching (1 dph) to adulthood, spanning the critical period for song learning (20 and 65 dph). We identified extensive transcriptional neurodevelopmental changes during postnatal telencephalon development. DNA methylation was very low, yet increased over time, particularly in song control nuclei. Only a small fraction of the massive differential expression in the developing zebra finch telencephalon could be explained by differential CpG and CpH DNA methylation. However, a strong association between DNA methylation and age-dependent gene expression was found for various transcription factors (i.e., OTX2, AR, and FOS) involved in neurodevelopment. Incomplete dosage compensation, independent of DNA methylation, was found to be largely responsible for sexually dimorphic gene expression, with dosage compensation increasing throughout life. In conclusion, our results indicate that DNA methylation regulates neurodevelopmental gene expression dynamics through steering transcription factor activity, but does not explain sexually dimorphic gene expression patterns in zebra finch telencephalon.

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