scholarly journals Synaptic and peptidergic connectome of a neurosecretory centre in the annelid brain

2017 ◽  
Author(s):  
Elizabeth A. Williams ◽  
Csaba Verasztó ◽  
Sanja Jasek ◽  
Markus Conzelmann ◽  
Réza Shahidi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Electron Microscopy ◽  
Cell Types ◽  
Peptide Receptor ◽  
Neurosecretory Neurons ◽  
Platynereis Dumerilii ◽  
The Brain ◽  
Gene Expression Mapping ◽  
Synaptic Signalling

AbstractNeurosecretory centres in animal brains use peptidergic signalling to influence physiology and behaviour. Understanding neurosecretory centre function requires mapping cell types, synapses, and peptidergic networks. Here we use electron microscopy and gene expression mapping to analyse the synaptic and peptidergic connectome of an entire neurosecretory centre. We mapped 78 neurosecretory neurons in the brain of larval Platynereis dumerilii, a marine annelid. These neurons form an anterior neurosecretory organ expressing many neuropeptides, including hypothalamic peptide orthologues and their receptors. Analysis of peptide-receptor pairs revealed sparsely connected networks linking specific neuronal subsets. We experimentally analysed one peptide-receptor pair and found that a neuropeptide can couple neurosecretory and synaptic brain signalling. Our study uncovered extensive non-synaptic signalling within a neurosecretory centre and its connection to the synaptic brain.

scholarly journals Synaptic and peptidergic connectome of a neurosecretory center in the annelid brain

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Elizabeth A Williams ◽  
Csaba Verasztó ◽  
Sanja Jasek ◽  
Markus Conzelmann ◽  
Réza Shahidi ◽  
...  
Keyword(s):  
Cell Types ◽  
Peptide Receptor ◽  
Behavior Understanding ◽  
Transmission Electron ◽  
Neurosecretory Neurons ◽  
Platynereis Dumerilii ◽  
Cell Transcriptome ◽  
Single Cell Transcriptome ◽  
And Behavior ◽  
The Brain

Neurosecretory centers in animal brains use peptidergic signaling to influence physiology and behavior. Understanding neurosecretory center function requires mapping cell types, synapses, and peptidergic networks. Here we use transmission electron microscopy and gene expression mapping to analyze the synaptic and peptidergic connectome of an entire neurosecretory center. We reconstructed 78 neurosecretory neurons and mapped their synaptic connectivity in the brain of larval Platynereis dumerilii, a marine annelid. These neurons form an anterior neurosecretory center expressing many neuropeptides, including hypothalamic peptide orthologs and their receptors. Analysis of peptide-receptor pairs in spatially mapped single-cell transcriptome data revealed sparsely connected networks linking specific neuronal subsets. We experimentally analyzed one peptide-receptor pair and found that a neuropeptide can couple neurosecretory and synaptic brain signaling. Our study uncovered extensive networks of peptidergic signaling within a neurosecretory center and its connection to the synaptic brain.

scholarly journals Glucocorticoid receptor action in metabolic and neuronal function

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1208 ◽  
Author(s):  
Michael J. Garabedian ◽  
Charles A. Harris ◽  
Freddy Jeanneteau
Keyword(s):  
Gene Expression ◽  
Glucocorticoid Receptor ◽  
Metabolic Diseases ◽  
Cell Types ◽  
Health And Disease ◽  
And Behavior ◽  
External Signals ◽  
The Brain

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them.

scholarly journals Systematic Gene Expression Mapping Clusters Nuclear Receptors According to Their Function in the Brain

Cell ◽  
2007 ◽  
Vol 131 (2) ◽  
pp. 405-418 ◽  
Author(s):  
Françoise Gofflot ◽  
Nathalie Chartoire ◽  
Laurent Vasseur ◽  
Sami Heikkinen ◽  
Doulaye Dembele ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nuclear Receptors ◽  
The Brain ◽  
Gene Expression Mapping

scholarly journals Tanycyte-independent control of hypothalamic leptin signaling

2019 ◽  
Author(s):  
Sooyeon Yoo ◽  
David Cha ◽  
Dong Won Kim ◽  
Thanh V. Hoang ◽  
Seth Blackshaw
Keyword(s):  
Gene Expression ◽  
Single Molecule ◽  
Leptin Receptor ◽  
Cell Types ◽  
Leptin Signaling ◽  
And Function ◽  
Induced Changes ◽  
The Brain ◽  
Specific Deletion

AbstractLeptin is secreted by adipocytes to regulate appetite and body weight. Recent studies have reported that tanycytes actively transport circulating leptin across the brain barrier into the hypothalamus, and are required for normal levels of hypothalamic leptin signaling. However, direct evidence for leptin receptor (LepR) expression is lacking, and the effect of tanycyte-specific deletion of LepR has not been investigated. In this study, we analyze the expression and function of the tanycytic LepR in mice. Using single-molecule fluorescent in situ hybridization (smfISH), RT-qPCR, single-cell RNA sequencing (scRNA-Seq), and selective deletion of the LepR in tanycytes, we are unable to detect expression of LepR in the tanycytes. Tanycyte-specific deletion of LepR likewise did not affect leptin-induced pSTAT3 expression in hypothalamic neurons, regardless of whether leptin was delivered by intraperitoneal or intracerebroventricular injection. Finally, we use activity-regulated scRNA-Seq (act-Seq) to comprehensively profile leptin-induced changes in gene expression in all cell types in mediobasal hypothalamus. Clear evidence for leptin signaling is only seen in endothelial cells and subsets of neurons, although virtually all cell types show leptin-induced changes in gene expression. We thus conclude that LepR expression in tanycytes is either absent or undetectably low, that tanycytes do not directly regulate hypothalamic leptin signaling through a LepR-dependent mechanism, and that leptin regulates gene expression in diverse hypothalamic cell types through both direct and indirect mechanisms.

scholarly journals Transposon-mediated, cell type-specific transcription factor recording in the mouse brain

2019 ◽  
Author(s):  
Alexander J. Cammack ◽  
Arnav Moudgil ◽  
Tomas Lagunas ◽  
Michael J. Vasek ◽  
Mark Shabsovich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mouse Brain ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Mouse Tissue ◽  
Specific Cell ◽  
Cell Type ◽  
Cell Fate Decisions ◽  
Cell Type Specific ◽  
The Brain

AbstractTranscription factors (TFs) play a central role in the regulation of gene expression, controlling everything from cell fate decisions to activity dependent gene expression. However, widely-used methods for TF profiling in vivo (e.g. ChIP-seq) yield only an aggregated picture of TF binding across all cell types present within the harvested tissue; thus, it is challenging or impossible to determine how the same TF might bind different portions of the genome in different cell types, or even to identify its binding events at all in rare cell types in a complex tissue such as the brain. Here we present a versatile methodology, FLEX Calling Cards, for the mapping of TF occupancy in specific cell types from heterogenous tissues. In this method, the TF of interest is fused to a hyperactive piggyBac transposase (hypPB), and this bipartite gene is delivered, along with donor transposons, to mouse tissue via a Cre-dependent adeno-associated virus (AAV). The fusion protein is expressed in Cre-expressing cells where it inserts transposon “Calling Cards” near to TF binding sites. These transposons permanently mark TF binding events and can be mapped using high-throughput sequencing. Alternatively, unfused hypPB interacts with and records the binding of the super enhancer (SE)-associated bromodomain protein, Brd4. To demonstrate the FLEX Calling Card method, we first show that donor transposon and transposase constructs can be efficiently delivered to the postnatal day 1 (P1) mouse brain with AAV and that insertion profiles report TF occupancy. Then, using a Cre-dependent hypPB virus, we show utility of this tool in defining cell type-specific TF profiles in multiple cell types of the brain. This approach will enable important cell type-specific studies of TF-mediated gene regulation in the brain and will provide valuable insights into brain development, homeostasis, and disease.

scholarly journals Gene expression in the developing nemertean brain indicates convergent evolution of complex brains in Spiralia

2021 ◽  
Author(s):  
Ludwik Gąsiorowski ◽  
Aina Børve ◽  
Irina A. Cherneva ◽  
Andrea Orús-Alcalde ◽  
Andreas Hejnol
Keyword(s):  
Gene Expression ◽  
Neural Development ◽  
Cell Types ◽  
Major Elements ◽  
Mushroom Bodies ◽  
Animal Group ◽  
Evolutionary Origins ◽  
The Moment ◽  
Cerebral Organ ◽  
The Brain

AbstractBackgroundNemertea is a clade of worm-like animals, which belongs to a larger animal group called Spiralia (together with e.g. annelids, flatworms and mollusks). Many of the nemertean species possess a complex central nervous system (CNS) with a prominent brain, and elaborated chemosensory and neuroglandular cerebral organs, which have been suggested as homologues to the annelid mushroom bodies. In order to understand the developmental and evolutionary origins of complex nemertean brain, we investigated details of neuroanatomy and gene expression in the brain and cerebral organs of the juveniles of nemertean Lineus ruber.ResultsIn the hatched juveniles the CNS is already composed of all major elements present in the adults, including the brain (with dorsal and ventral lobes), paired longitudinal lateral nerve cords and an unpaired dorsal nerve cord. The TEM investigation of the juvenile cerebral organ revealed that the structure is already composed of several distinct cell types present also in the adults. We further investigated the expression of twelve transcription factors commonly used as brain and cell type markers in bilaterian brains, including genes specific for annelid mushroom bodies. The expression of the investigated genes in the brain is region-specific and divides the entire organ into several molecularly distinct areas, partially overlapping with the morphological compartments. Additionally, we detected expression of mushroom body specific genes in the developing cerebral organs.ConclusionsAt the moment of hatching, the juveniles of L. ruber already have a similar neuroarchitecture as adult worms, which suggests that further neural development is mostly related with increase in the size but not in complexity. Comparison in the gene expression between L. ruber and the annelid Platynereis dumerilii and other spiralians, indicates that the complex brains present in those two species evolved convergently by independent expansion of non-homologues regions of the simpler brain present in their common ancestor. The similarities in gene expression in mushroom bodies and cerebral organs might be a result of the convergent recruitment of the same genes into patterning of non-homologues organs or the results of more complicated evolutionary processes, in which conserved and novel cell types contribute to the non-homologues structures.

Gene Expression in Neuronal Disease

2009 ◽  
Vol 37 (6) ◽  
pp. 1261-1262 ◽  
Author(s):  
Ian C. Wood ◽  
Nicola K. Gray ◽  
Lesley Jones
Keyword(s):  
Gene Expression ◽  
Rna Processing ◽  
Cell Types ◽  
Single Step ◽  
The Body ◽  
Regulation Of Transcription ◽  
Neuronal Disease ◽  
Inappropriate Gene Expression ◽  
The Brain ◽  
Complex Organ

The brain is the most complex organ of the body and it contains the greatest diversity of cell types. Collectively, the cells within the brain express the greatest number of genes encoded within our genome. Inappropriate gene expression within these cells plays a fundamental role in many neuronal diseases. Illuminating the mechanisms responsible for gene expression is key to understanding these diseases. Because of the complexity, however, there is still much to understand about the mechanisms responsible for gene expression in the brain. There are many steps required for a protein to be generated from a gene, and groups who focus on gene expression normally study a single step such as regulation of transcription, mechanisms of RNA processing or control of translation. To address this, experts were brought together at the Gene Expression in Neuronal Disease meeting in Cardiff. This forum provided the latest insights into specific stages of gene expression in the brain and encompassed the complete pathway from DNA to protein. The present article summarizes the meeting talks and related papers in this issue of Biochemical Society Transactions.

scholarly journals EM connectomics reveals axonal target variation in a sequence-generating network

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Jörgen Kornfeld ◽  
Sam E Benezra ◽  
Rajeevan T Narayanan ◽  
Fabian Svara ◽  
Robert Egger ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Cell Types ◽  
Cortical Region ◽  
Inhibitory Interneurons ◽  
Underlying Network ◽  
Block Face ◽  
Sequential Activation ◽  
Neural Sequences ◽  
The Brain ◽  
Inhibitory Networks

The sequential activation of neurons has been observed in various areas of the brain, but in no case is the underlying network structure well understood. Here we examined the circuit anatomy of zebra finch HVC, a cortical region that generates sequences underlying the temporal progression of the song. We combined serial block-face electron microscopy with light microscopy to determine the cell types targeted by HVC(RA) neurons, which control song timing. Close to their soma, axons almost exclusively targeted inhibitory interneurons, consistent with what had been found with electrical recordings from pairs of cells. Conversely, far from the soma the targets were mostly other excitatory neurons, about half of these being other HVC(RA) cells. Both observations are consistent with the notion that the neural sequences that pace the song are generated by global synaptic chains in HVC embedded within local inhibitory networks.

Somitomeres: mesodermal segments of vertebrate embryos

Development ◽  
1988 ◽  
Vol 104 (Supplement) ◽  
pp. 209-220 ◽  
Author(s):  
Antone G. Jacobson
Keyword(s):  
Electron Microscopy ◽  
Chick Embryo ◽  
Cell Types ◽  
Paraxial Mesoderm ◽  
Tail Bud ◽  
Snapping Turtle ◽  
Vertebrate Embryos ◽  
The Brain ◽  
Brain Parts ◽  
Scanning Electron

Well before the somites form, the paraxial mesoderm of vertebrate embryos is segmented into somitomeres. When newly formed, somitomeres are patterned arrays of mesenchymal cells, arranged into squat, bilaminar discs. The dorsal and ventral faces of these discs are composed of concentric rings of cells. Somitomeres are formed along the length of the embryo during gastrulation, and in the segmental plate and tail bud at later stages. They form in strict cranial to caudal order. They appear in bilateral pairs, just lateral to Hensen's node in the chick embryo. When the nervous system begins to form, the brain parts and neuromeres are in a consistent relationship to the somitomeres. Somitomeres first appear in the head, and the cranial somitomeres do not become somites, but disperse to contribute to the head the same cell types contributed by somites in the trunk region. In the trunk and tail, somitomeres gradually condense and epithelialize to become somites. Models of vertebrate segmentation must now take into account the early presence of these new morphological units, the somitomeres. Somitomeres were discovered in the head of the chick embryo (Meier, 1979), with the use of stereo scanning electron microscopy. The old question of whether the heads of the craniates are segmented is now settled, at least for the paraxial mesoderm. Somitomeres have now been identified in the embryos of a chick, quail, mouse, snapping turtle, newt, anuran (Xenopus) and a teleost (the medaka). In all forms studied, the first pair of somitomeres abut the prosencephalon but caudal to that, for each tandem pair of somitomeres in the amniote and teleost, there is but one somitomere in the amphibia. The mesodermal segments of the shark embryo are arranged like those of the amphibia.

scholarly journals Substantial DNA methylation differences between two major neuronal subtypes in human brain

2015 ◽  
Vol 44 (6) ◽  
pp. 2593-2612 ◽  
Author(s):  
Alexey Kozlenkov ◽  
Minghui Wang ◽  
Panos Roussos ◽  
Sergei Rudchenko ◽  
Mihaela Barbu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Cell Types ◽  
Cpg Methylation ◽  
Projection Neurons ◽  
Specific Gene ◽  
Cpg Sites ◽  
Gaba Neurons ◽  
The Brain

Abstract The brain is built from a large number of cell types which have been historically classified using location, morphology and molecular markers. Recent research suggests an important role of epigenetics in shaping and maintaining cell identity in the brain. To elucidate the role of DNA methylation in neuronal differentiation, we developed a new protocol for separation of nuclei from the two major populations of human prefrontal cortex neurons—GABAergic interneurons and glutamatergic (GLU) projection neurons. Major differences between the neuronal subtypes were revealed in CpG, non-CpG and hydroxymethylation (hCpG). A dramatically greater number of undermethylated CpG sites in GLU versus GABA neurons were identified. These differences did not directly translate into differences in gene expression and did not stem from the differences in hCpG methylation, as more hCpG methylation was detected in GLU versus GABA neurons. Notably, a comparable number of undermethylated non-CpG sites were identified in GLU and GABA neurons, and non-CpG methylation was a better predictor of subtype-specific gene expression compared to CpG methylation. Regions that are differentially methylated in GABA and GLU neurons were significantly enriched for schizophrenia risk loci. Collectively, our findings suggest that functional differences between neuronal subtypes are linked to their epigenetic specification.

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