scholarly journals Developmental Accumulation of Gene Body and Transposon Non-CpG Methylation in the Zebrafish Brain

2021 ◽  
Vol 9 ◽  
Author(s):  
Samuel E. Ross ◽  
Daniel Hesselson ◽  
Ozren Bogdanovic
Keyword(s):  
Nervous System ◽  
Transcriptional Repression ◽  
System Development ◽  
Evolutionary Conservation ◽  
Nervous System Development ◽  
Zebrafish Brain ◽  
Zebrafish Larvae ◽  
And Function ◽  
Cg Dinucleotides ◽  
Embryonic Brain Development

DNA methylation predominantly occurs at CG dinucleotides in vertebrate genomes; however, non-CG methylation (mCH) is also detectable in vertebrate tissues, most notably in the nervous system. In mammals it is well established that mCH is targeted to CAC trinucleotides by DNMT3A during nervous system development where it is enriched in gene bodies and associated with transcriptional repression. Nevertheless, the conservation of developmental mCH accumulation and its deposition by DNMT3A is largely unexplored and has yet to be functionally demonstrated in other vertebrates. In this study, by analyzing DNA methylomes and transcriptomes of zebrafish brains, we identified enrichment of mCH at CAC trinucleotides (mCAC) at defined transposon motifs as well as in developmentally downregulated genes associated with developmental and neural functions. We further generated and analyzed DNA methylomes and transcriptomes of developing zebrafish larvae and demonstrated that, like in mammals, mCH accumulates during post-embryonic brain development. Finally, by employing CRISPR/Cas9 technology, we unraveled a conserved role for Dnmt3a enzymes in developmental mCAC deposition. Overall, this work demonstrates the evolutionary conservation of developmental mCH dynamics and highlights the potential of zebrafish as a model to study mCH regulation and function during normal and perturbed development.

scholarly journals Developmental accumulation of gene body and transposon non-CpG methylation in the zebrafish brain

2020 ◽  
Author(s):  
Samuel E Ross ◽  
Daniel Hesselson ◽  
Ozren Bogdanovic
Keyword(s):  
Nervous System ◽  
Transcriptional Repression ◽  
System Development ◽  
Evolutionary Conservation ◽  
Nervous System Development ◽  
Zebrafish Brain ◽  
Zebrafish Larvae ◽  
And Function ◽  
Cg Dinucleotides ◽  
Embryonic Brain Development

DNA methylation predominantly occurs at CG dinucleotides in vertebrate genomes; however, non-CG methylation (mCH) is also detectable in vertebrate tissues, most notably in the nervous system. In mammals it is well established that mCH is targeted to CAC trinucleotides by DNMT3A during nervous system development where it is enriched in gene bodies and associated with transcriptional repression. However, the conservation of developmental mCH accumulation and its deposition by DNMT3A is largely unexplored and has yet to be functionally demonstrated in other vertebrates. In this study, by analyzing DNA methylomes and transcriptomes of zebrafish brains, we identified enrichment of mCH at CAC trinucleotides (mCAC) at defined transposon motifs as well as in developmentally downregulated genes associated with developmental and neural functions. We further generated and analyzed DNA methylomes and transcriptomes of developing zebrafish larvae and demonstrated that, like in mammals, mCH accumulates during post-embryonic brain development. Finally, by employing CRISPR/Cas9 technology, we unraveled a conserved role for Dnmt3a enzymes in developmental mCAC deposition. Overall, this work demonstrates the evolutionary conservation of developmental mCH dynamics and highlights the potential of zebrafish as a model to study mCH regulation and function during normal and perturbed development.

scholarly journals Neurons interact with the microbiome: an evolutionary-informed perspective

Neuroforum ◽  
2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Christoph Giez ◽  
Alexander Klimovich ◽  
Thomas C. G. Bosch
Keyword(s):  
Nervous System ◽  
Neural Circuits ◽  
Current Knowledge ◽  
System Development ◽  
Nervous System Development ◽  
Comprehensive Understanding ◽  
Strategic Model ◽  
Microbe Interactions ◽  
Host Microbe Interactions ◽  
And Function

Abstract Animals have evolved within the framework of microbes and are constantly exposed to diverse microbiota. Microbes colonize most, if not all, animal epithelia and influence the activity of many organs, including the nervous system. Therefore, any consideration on nervous system development and function in the absence of the recognition of microbes will be incomplete. Here, we review the current knowledge on the nervous systems of Hydra and its role in the host–microbiome communication. We show that recent advances in molecular and imaging methods are allowing a comprehensive understanding of the capacity of such a seemingly simple nervous system in the context of the metaorganism. We propose that the development, function and evolution of neural circuits must be considered in the context of host–microbe interactions and present Hydra as a strategic model system with great basic and translational relevance for neuroscience.

scholarly journals A loss-of-function homozygous mutation in DDX59 implicates a conserved DEAD-box RNA helicase in nervous system development and function

2017 ◽  
Vol 39 (2) ◽  
pp. 187-192 ◽  
Author(s):  
Vincenzo Salpietro ◽  
Stephanie Efthymiou ◽  
Andreea Manole ◽  
Bhawana Maurya ◽  
Sarah Wiethoff ◽  
...  
Keyword(s):  
Nervous System ◽  
System Development ◽  
Rna Helicase ◽  
Nervous System Development ◽  
Homozygous Mutation ◽  
Loss Of Function ◽  
Dead Box ◽  
And Function

scholarly journals Genetic Basis of Variation in Cocaine and Methamphetamine Consumption in Outbred Populations of Drosophila melanogaster

2021 ◽  
Author(s):  
Brandon M. Baker ◽  
Mary Anna Carbone ◽  
Wen Huang ◽  
Robert R. H. Anholt ◽  
Trudy F. C. Mackay
Keyword(s):  
Nervous System ◽  
Drosophila Melanogaster ◽  
Genetic Basis ◽  
Genetic Model ◽  
System Development ◽  
Gene Interaction ◽  
Nervous System Development ◽  
Drug Consumption ◽  
Human Populations ◽  
And Function

AbstractWe used Drosophila melanogaster to map the genetic basis of naturally occurring variation in voluntary consumption of cocaine and methamphetamine. We derived an outbred advanced intercross population (AIP) from 37 sequenced inbred wild-derived lines of the Drosophila melanogaster Genetic Reference Panel (DGRP), which are maximally genetically divergent, have minimal residual heterozygosity, are not segregating for common inversions, and are not infected with Wolbachia pipientis. We assessed consumption of sucrose, methamphetamine-supplemented sucrose and cocaine-supplemented sucrose, and found considerable phenotypic variation for consumption of both drugs, in both sexes. We performed whole genome sequencing and extreme QTL mapping on the top 10% of consumers for each replicate, sex and condition, and an equal number of randomly selected flies. We evaluated changes in allele frequencies among high consumers and control flies and identified 3,033 variants significantly (P < 1.9 × 10-8) associated with increased consumption, located in or near 1,962 genes. Many of these genes are associated with nervous system development and function, and 77 belong to a known gene-gene interaction subnetwork. We assessed the effects of RNA interference (RNAi) on drug consumption for 22 candidate genes; 17 had a significant effect in at least one sex. We constructed allele-specific AIPs which were homozygous for alternative candidate alleles for 10 SNPs and measured average consumption for each population; nine SNPs had significant effects in at least one sex. The genetic basis of voluntary drug consumption in Drosophila is polygenic and implicates genes with human orthologs and associated variants with sex- and drug-specific effects.Significance StatementThe use of cocaine and methamphetamine presents significant socioeconomic problems. However, identifying the genetic underpinnings that determine susceptibility to substance use is challenging in human populations. The fruit fly, Drosophila melanogaster, presents a powerful genetic model since we can control the genetic background and environment, 75% of disease-causing genes in humans have a fly counterpart, and flies - like humans - exhibit adverse effects upon cocaine and methamphetamine exposure. We showed that the genetic architecture underlying variation in voluntary cocaine and methamphetamine consumption differs between sexes and is dominated by variants in genes associated with connectivity and function of the nervous system. Results obtained from the Drosophila gene discovery model can guide studies on substance abuse susceptibility in human populations.

scholarly journals Glia as architects of central nervous system formation and function

Science ◽  
2018 ◽  
Vol 362 (6411) ◽  
pp. 181-185 ◽  
Author(s):  
Nicola J. Allen ◽  
David A. Lyons
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Biology ◽  
Radial Glia ◽  
System Development ◽  
Nervous System Development ◽  
Dynamic Monitoring ◽  
Oligodendrocyte Progenitor Cells ◽  
System Formation ◽  
And Function

Glia constitute roughly half of the cells of the central nervous system (CNS) but were long-considered to be static bystanders to its formation and function. Here we provide an overview of how the diverse and dynamic functions of glial cells orchestrate essentially all aspects of nervous system formation and function. Radial glia, astrocytes, oligodendrocyte progenitor cells, oligodendrocytes, and microglia each influence nervous system development, from neuronal birth, migration, axon specification, and growth through circuit assembly and synaptogenesis. As neural circuits mature, distinct glia fulfill key roles in synaptic communication, plasticity, homeostasis, and network-level activity through dynamic monitoring and alteration of CNS structure and function. Continued elucidation of glial cell biology, and the dynamic interactions of neurons and glia, will enrich our understanding of nervous system formation, health, and function.

scholarly journals Selenoproteins in Nervous System Development and Function

2014 ◽  
Vol 161 (3) ◽  
pp. 231-245 ◽  
Author(s):  
Matthew W. Pitts ◽  
China N. Byrns ◽  
Ashley N. Ogawa-Wong ◽  
Penny Kremer ◽  
Marla J. Berry
Keyword(s):  
Nervous System ◽  
System Development ◽  
Nervous System Development ◽  
And Function

scholarly journals Role of Nuclear Receptors in Central Nervous System Development and Associated Diseases

2015 ◽  
Vol 9s2 ◽  
pp. JEN.S25480 ◽  
Author(s):  
Ana Ana Maria ◽  
Moreno-Ramos Oscar Andréas ◽  
Neena B. Haider
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Nuclear Receptors ◽  
System Development ◽  
Nuclear Hormone Receptor ◽  
Nervous System Development ◽  
Wide Range ◽  
And Function ◽  
The Impact

The nuclear hormone receptor (NHR) superfamily is composed of a wide range of receptors involved in a myriad of important biological processes, including development, growth, metabolism, and maintenance. Regulation of such wide variety of functions requires a complex system of gene regulation that includes interaction with transcription factors, chromatin-modifying complex, and the proper recognition of ligands. NHRs are able to coordinate the expression of genes in numerous pathways simultaneously. This review focuses on the role of nuclear receptors in the central nervous system and, in particular, their role in regulating the proper development and function of the brain and the eye. In addition, the review highlights the impact of mutations in NHRs on a spectrum of human diseases from autism to retinal degeneration.

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