Recombineering Hunchback identifies two conserved domains required to maintain neuroblast competence and specify early-born neuronal identity

AbstractThe diversity reflected by >100 different neural cell types fundamentally contributes to brain function and a central idea is that neuronal identity can be inferred from genetic information. Recent large-scale transcriptomic assays seem to confirm this hypothesis, but a lack of morphological information has limited the identification of several known cell types. In this study, we used single-cell RNA-seq in morphologically identified parvalbumin interneurons (PV-INs), and studied their transcriptomic states in the morphological, physiological, and developmental domains. Overall, we find high transcriptomic similarity among PV-INs, with few genes showing divergent expression between morphologically different types. Furthermore, PV-INs show a uniform synaptic cell adhesion molecule (CAM) profile, suggesting that CAM expression in mature PV cells does not reflect wiring specificity after development. Together, our results suggest that while PV-INs differ in anatomy and in vivo activity, their continuous transcriptomic and homogenous biophysical landscapes are not predictive of these distinct identities.

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Cortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination

Nature Communications ◽

10.1038/s41467-021-25035-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Cody L. Call ◽

Dwight E. Bergles

Keyword(s):

Cortical Neurons ◽

Regional Differences ◽

Brain Regions ◽

Axon Diameter ◽

Neuronal Identity ◽

Cortical Areas ◽

Myelin Sheaths ◽

Parvalbumin Interneurons ◽

Selection Of

ABSTRACTAxons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; however, the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. Here we show that myelination patterns of seven distinct neuron subtypes in somatosensory cortex are influenced by both axon diameter and neuronal identity. Preference for myelination of parvalbumin interneurons was preserved between cortical areas with varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis. By imaging loss and regeneration of myelin sheaths in vivo we show that myelin distribution on individual axons was altered but overall myelin content on distinct neuron subtypes was restored. Our findings suggest that local changes in myelination are tolerated, allowing regenerated oligodendrocytes to restore myelin content on distinct neurons through opportunistic selection of axons.

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Nuclear Receptor NR5A2 Promotes Neuronal Identity in the Adult Hippocampus

Molecular Neurobiology ◽

10.1007/s12035-020-02222-8 ◽

2021 ◽

Author(s):

Matina Tsampoula ◽

Isaak Tarampoulous ◽

Ivi Antoniadou ◽

Yassemi Koutmani ◽

Dimitrios Gkikas ◽

...

Keyword(s):

Nuclear Receptor ◽

Neuronal Identity ◽

Adult Hippocampus

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Mutational hotspots and conserved domains of SARS-CoV-2 genome in African population

Beni-Suef University Journal of Basic and Applied Sciences ◽

10.1186/s43088-021-00102-1 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Olabode E. Omotoso ◽

Ayoade D. Babalola ◽

Amira Matareek

Keyword(s):

Global Economy ◽

African Population ◽

The Novel ◽

Conserved Domains ◽

Nucleocapsid Proteins ◽

Genome Variability ◽

Promising Strategy ◽

Mutational Hotspots ◽

Novel Coronavirus ◽

Complete Protein

Abstract Background Since outbreak in December 2019, the highly infectious and pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over a million deaths globally. With increasing burden, the novel coronavirus has posed a dire threat to public health, social interaction, and global economy. Mutations in the SARS-CoV-2 genome are moderately evolving which might have contributed to its genome variability, transmission, replication efficiency, and virulence in different regions of the world. Results The present study elucidated the mutational landscape in the SARS-CoV-2 genome among the African populace, which may have contributed to the virulence, spread, and pathogenicity observed in the region. A total of 3045 SARS-CoV-2 complete protein sequences with the reference viral sequence (EPI_ISL_402124) were mined and analyzed. SARS-CoV-2 ORF1ab, spike, ORF3, ORF8, and nucleocapsid proteins were observed as mutational hotspots in the African population and may be of keen interest in understanding the viral host relationship, while there is conservation in the ORF6, ORF7a, ORF7b, ORF10, envelope, and membrane proteins. Conclusions The accumulation of moderate mutations (though slowly), in the SARS-CoV-2 genome as seen in this present study, could be a promising strategy to develop antiviral drugs or vaccines. These antiviral interventions should target viral conserved domains and host cellular proteins and/or receptors involved in viral invasion and replication to avoid a new viral wave due to drug resistance and vaccine evasion.

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Thebric à braclocus consists of two paralogous genes encoding BTB/POZ domain proteins and acts as a homeotic and morphogenetic regulator of imaginal development inDrosophila

Development ◽

10.1242/dev.129.10.2419 ◽

2002 ◽

Vol 129 (10) ◽

pp. 2419-2433 ◽

Cited By ~ 6

Author(s):

Jean-Louis Couderc ◽

Dorothea Godt ◽

Susan Zollman ◽

Jiong Chen ◽

Michelle Li ◽

...

Keyword(s):

Tissue Distribution ◽

Nuclear Protein ◽

Drosophila Species ◽

Sexually Dimorphic ◽

Conserved Domains ◽

Gene Dose ◽

Highly Sensitive ◽

Genes Encoding ◽

Redundant Functions ◽

Related Morphology

The bric à brac (bab) locus acts as a homeotic and morphogenetic regulator in the development of ovaries, appendages and the abdomen. It consists of two structurally and functionally related genes, bab1 and bab2, each of which encodes a single nuclear protein. Bab1 and Bab2 have two conserved domains in common, a BTB/POZ domain and a Psq domain, a motif that characterizes a subfamily of BTB/POZ domain proteins in Drosophila. The tissue distribution of Bab1 and Bab2 overlaps, with Bab1 being expressed in a subpattern of Bab2. Analysis of a series of mutations indicates that the two bab genes have synergistic, distinct and redundant functions during imaginal development. Interestingly, several reproduction-related traits that are sexually dimorphic or show diversity among Drosophila species are highly sensitive to changes in the bab gene dose, suggesting that alterations in bab activity may contribute to evolutionary modification of sex-related morphology.

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Pathogenic tau disrupts the cellular program that maintains neuronal identity

10.1101/2021.03.05.434166 ◽

2021 ◽

Author(s):

Adrian Beckmann ◽

Paulino Ramirez ◽

Maria Gamez ◽

William J. Ray ◽

Bess Frost

Keyword(s):

Alzheimer’S Disease ◽

Cell Cycle ◽

Alzheimer's Disease ◽

Epithelial Mesenchymal Transition ◽

Tumor Formation ◽

Therapeutic Approaches ◽

Nuclear Pleomorphism ◽

Mesenchymal Transition ◽

Neuronal Identity ◽

Cell Cycle Activation

AbstractNeurons in human Alzheimer’s disease acquire phenotypes that are also present in various cancers, including over-stabilization of the cytoskeleton, nuclear pleomorphism, decondensation of constitutive heterochromatin, and aberrant activation of the cell cycle. Unlike in cancer, in which cell cycle activation drives tumor formation, activation of the cell cycle in post-mitotic neurons is sufficient to induce neuronal death. Multiple lines of evidence suggest that abortive cell cycle activation is a consequence of pathogenic forms of tau, a protein that drives neurodegeneration in Alzheimer’s disease and related “tauopathies.” We have combined network analysis of human Alzheimer’s disease and mouse tauopathy with mechanistic studies in Drosophila to discover that pathogenic forms of tau drive abortive cell cycle activation by disrupting the cellular program that maintains neuronal identity. Mechanistically, we identify Moesin, a prognostic biomarker for cancer and mediator of the epithelial-mesenchymal transition (EMT), as a major effector of tau-induced neurotoxicity. We find that aberrant activation of Moesin in neurons acts through the actin cytoskeleton to dysregulate the cellular program that maintains neuronal identity. Our study identifies mechanistic parallels between tauopathy and cancer and sets the stage for novel therapeutic approaches.

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Purification of arginase from Aspergillus nidulans.

Acta Biochimica Polonica ◽

10.18388/abp.1994_4700 ◽

1994 ◽

Vol 41 (4) ◽

pp. 467-471 ◽

Cited By ~ 4

Author(s):

A Dzikowska ◽

J P Le Caer ◽

P Jonczyk ◽

P Wëgleński

Keyword(s):

Saccharomyces Cerevisiae ◽

Neurospora Crassa ◽

Molecular Mass ◽

Nitrogen Source ◽

Aspergillus Nidulans ◽

Sole Nitrogen Source ◽

Mass Ratio ◽

Conserved Domains ◽

Native Molecular Mass ◽

High Degree

Arginase (EC 3.5.3.1) of Aspergillus nidulans, the enzyme which enables the fungus to use arginine as the sole nitrogen source was purified to homogeneity. Molecular mass of the purified arginase subunit is 40 kDa and is similar to that reported for the Neurospora crassa (38.3 kDa) and Saccharomyces cerevisiae (39 kDa) enzymes. The native molecular mass of arginase is 125 kDa. The subunit/native molecular mass ratio suggests a trimeric form of the protein. The arginase protein was cleaved and partially sequenced. Two out of the six polypeptides sequenced show a high degree of homology to conserved domains in arginases from other species.

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