scholarly journals Ordered patterning of the sensory system is susceptible to stochastic features of gene expression

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Ritika Giri ◽  
Dimitrios K Papadopoulos ◽  
Diana M Posadas ◽  
Hemanth K Potluri ◽  
Pavel Tomancak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Sensory System ◽  
Critical Feature ◽  
Environmental Signals ◽  
Microrna Regulation ◽  
Biochemical Processes ◽  
Genomic Location ◽  
In Trans ◽  
The Brain

Sensory neuron numbers and positions are precisely organized to accurately map environmental signals in the brain. This precision emerges from biochemical processes within and between cells that are inherently stochastic. We investigated impact of stochastic gene expression on pattern formation, focusing on senseless (sens), a key determinant of sensory fate in Drosophila. Perturbing microRNA regulation or genomic location of sens produced distinct noise signatures. Noise was greatly enhanced when both sens alleles were present in homologous loci such that each allele was regulated in trans by the other allele. This led to disordered patterning. In contrast, loss of microRNA repression of sens increased protein abundance but not sensory pattern disorder. This suggests that gene expression stochasticity is a critical feature that must be constrained during development to allow rapid yet accurate cell fate resolution.

scholarly journals Ordered patterning of the sensory system is susceptible to stochastic features of gene expression

2019 ◽  
Author(s):  
Ritika Giri ◽  
Dimitrios K. Papadopoulos ◽  
Diana M. Posadas ◽  
Hemanth K. Potluri ◽  
Pavel Tomancak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Sensory System ◽  
Intrinsic Noise ◽  
Protein Abundance ◽  
Dependent Manner ◽  
Genomic Locus ◽  
Critical Feature ◽  
Environmental Signals ◽  
Microrna Regulation

AbstractSensory neuron numbers and positions are precisely organized to accurately map environmental signals in the brain. However, this precision must emerge from biochemical processes within and between cells that are stochastic. We measured intrinsic noise in senseless protein output, a key determinant of sensory fate, during Drosophila development. Perturbing microRNA regulation or genomic locus of senseless transcription produced distinct noise signatures. Genomic location altered protein stochasticity in an allelic-pairing dependent manner (transvection). This generated sensory pattern disorder without perturbing protein abundance. In contrast, loss of microRNA repression of senseless increased protein abundance but not sensory pattern disorder. This suggests that gene expression stochasticity is a critical feature that must be constrained during development to allow rapid yet accurate cell fate resolution.One Sentence SummaryLife on the Margin: balancing speed and accuracy during animal development.

scholarly journals Emerging Role of m6 A Methylome in Brain Development: Implications for Neurological Disorders and Potential Treatment

2021 ◽  
Vol 9 ◽  
Author(s):  
Godwin Sokpor ◽  
Yuanbin Xie ◽  
Huu P. Nguyen ◽  
Tran Tuoc
Keyword(s):  
Gene Expression ◽  
Brain Development ◽  
Cell Fate ◽  
Messenger Rna ◽  
Environmental Changes ◽  
Neurological Diseases ◽  
Regulation Of Gene Expression ◽  
Progenitor Cell Proliferation ◽  
And Function ◽  
The Brain

Dynamic modification of RNA affords proximal regulation of gene expression triggered by non-genomic or environmental changes. One such epitranscriptomic alteration in RNA metabolism is the installation of a methyl group on adenosine [N6-methyladenosine (m6A)] known to be the most prevalent modified state of messenger RNA (mRNA) in the mammalian cell. The methylation machinery responsible for the dynamic deposition and recognition of m6A on mRNA is composed of subunits that play specific roles, including reading, writing, and erasing of m6A marks on mRNA to influence gene expression. As a result, peculiar cellular perturbations have been linked to dysregulation of components of the mRNA methylation machinery or its cofactors. It is increasingly clear that neural tissues/cells, especially in the brain, make the most of m6A modification in maintaining normal morphology and function. Neurons in particular display dynamic distribution of m6A marks during development and in adulthood. Interestingly, such dynamic m6A patterns are responsive to external cues and experience. Specific disturbances in the neural m6A landscape lead to anomalous phenotypes, including aberrant stem/progenitor cell proliferation and differentiation, defective cell fate choices, and abnormal synaptogenesis. Such m6A-linked neural perturbations may singularly or together have implications for syndromic or non-syndromic neurological diseases, given that most RNAs in the brain are enriched with m6A tags. Here, we review the current perspectives on the m6A machinery and function, its role in brain development and possible association with brain disorders, and the prospects of applying the clustered regularly interspaced short palindromic repeats (CRISPR)–dCas13b system to obviate m6A-related neurological anomalies.

1805-P: Insulin Regulates a Broad Network of Gene Expression in the Brain to Regulated Brain Metabolism and Neurotransmission

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1805-P
Author(s):  
WEIKANG CAI ◽  
THIAGO M. BATISTA ◽  
RUBEN GARCIA MARTIN ◽  
ALFRED RAMIREZ ◽  
MASAHIRO KONISHI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Brain Metabolism ◽  
The Brain

scholarly journals Vibrionaceae core, shell and cloud genes are non-randomly distributed on Chr 1: An hypothesis that links the genomic location of genes with their intracellular placement

BMC Genomics ◽  
2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Cecilie Bækkedal Sonnenberg ◽  
Tim Kahlke ◽  
Peik Haugen
Keyword(s):  
Gene Expression ◽  
Expression Patterns ◽  
Fast Growth ◽  
Gene Copy ◽  
Distribution Data ◽  
Optimization Strategy ◽  
Gene Distribution ◽  
Fast Growing ◽  
Genomic Location ◽  
Growing Conditions

Abstract Background The genome of Vibrionaceae bacteria, which consists of two circular chromosomes, is replicated in a highly ordered fashion. In fast-growing bacteria, multifork replication results in higher gene copy numbers and increased expression of genes located close to the origin of replication of Chr 1 (ori1). This is believed to be a growth optimization strategy to satisfy the high demand of essential growth factors during fast growth. The relationship between ori1-proximate growth-related genes and gene expression during fast growth has been investigated by many researchers. However, it remains unclear which other gene categories that are present close to ori1 and if expression of all ori1-proximate genes is increased during fast growth, or if expression is selectively elevated for certain gene categories. Results We calculated the pangenome of all complete genomes from the Vibrionaceae family and mapped the four pangene categories, core, softcore, shell and cloud, to their chromosomal positions. This revealed that core and softcore genes were found heavily biased towards ori1, while shell genes were overrepresented at the opposite part of Chr 1 (i.e., close to ter1). RNA-seq of Aliivibrio salmonicida and Vibrio natriegens showed global gene expression patterns that consistently correlated with chromosomal distance to ori1. Despite a biased gene distribution pattern, all pangene categories contributed to a skewed expression pattern at fast-growing conditions, whereas at slow-growing conditions, softcore, shell and cloud genes were responsible for elevated expression. Conclusion The pangene categories were non-randomly organized on Chr 1, with an overrepresentation of core and softcore genes around ori1, and overrepresentation of shell and cloud genes around ter1. Furthermore, we mapped our gene distribution data on to the intracellular positioning of chromatin described for V. cholerae, and found that core/softcore and shell/cloud genes appear enriched at two spatially separated intracellular regions. Based on these observations, we hypothesize that there is a link between the genomic location of genes and their cellular placement.

scholarly journals Alternative splicing during mammalian organ development

2021 ◽  
Author(s):  
Pavel V. Mazin ◽  
Philipp Khaitovich ◽  
Margarida Cardoso-Moreira ◽  
Henrik Kaessmann
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Regulatory Networks ◽  
Organ Development ◽  
Functional Diversification ◽  
Mammalian Genomes ◽  
Species Comparisons ◽  
Time Specific ◽  
The Brain ◽  
Gene Expression Levels

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.

scholarly journals MiR-7 in Cancer Development

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 325
Author(s):  
Petra Korać ◽  
Mariastefania Antica ◽  
Maja Matulić
Keyword(s):  
Cell Fate ◽  
Dominant Role ◽  
Tumor Development ◽  
Mrna Translation ◽  
Cell Types ◽  
Fine Tuning ◽  
Non Coding Rna ◽  
Tumor Types ◽  
Different Cell Types ◽  
The Brain

MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.

scholarly journals LSD1 enzyme inhibitor TAK-418 unlocks aberrant epigenetic machinery and improves autism symptoms in neurodevelopmental disorder models

2021 ◽  
Vol 7 (11) ◽  
pp. eaba1187
Author(s):  
Rina Baba ◽  
Satoru Matsuda ◽  
Yuuichi Arakawa ◽  
Ryuji Yamada ◽  
Noriko Suzuki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enzyme Activity ◽  
Neurodevelopmental Disorders ◽  
Neurodevelopmental Disorder ◽  
Specific Inhibitor ◽  
Autism Spectrum ◽  
Poly I:C ◽  
Control Of Gene Expression ◽  
Epigenetic Machinery ◽  
The Brain

Persistent epigenetic dysregulation may underlie the pathophysiology of neurodevelopmental disorders, such as autism spectrum disorder (ASD). Here, we show that the inhibition of lysine-specific demethylase 1 (LSD1) enzyme activity normalizes aberrant epigenetic control of gene expression in neurodevelopmental disorders. Maternal exposure to valproate or poly I:C caused sustained dysregulation of gene expression in the brain and ASD-like social and cognitive deficits after birth in rodents. Unexpectedly, a specific inhibitor of LSD1 enzyme activity, 5-((1R,2R)-2-((cyclopropylmethyl)amino)cyclopropyl)-N-(tetrahydro-2H-pyran-4-yl)thiophene-3-carboxamide hydrochloride (TAK-418), almost completely normalized the dysregulated gene expression in the brain and ameliorated some ASD-like behaviors in these models. The genes modulated by TAK-418 were almost completely different across the models and their ages. These results suggest that LSD1 enzyme activity may stabilize the aberrant epigenetic machinery in neurodevelopmental disorders, and the inhibition of LSD1 enzyme activity may be the master key to recover gene expression homeostasis. TAK-418 may benefit patients with neurodevelopmental disorders.

scholarly journals Three‐dimensional multi‐gene expression maps reveal cell fate changes associated with laterality reversal of zebrafish habenula

2021 ◽  
Author(s):  
Guo‐Tzau Wang ◽  
He‐Yen Pan ◽  
Wei‐Han Lang ◽  
Yuan‐Ding Yu ◽  
Chang‐Huain Hsieh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Three Dimensional
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