Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Drosophila voltage-gated sodium channels are only expressed in active neurons and are localized to distal axonal initial segment-like domains

ABSTRACT: In multipolar vertebrate neurons, action potentials (AP) initiate close to the soma, at the axonal initial segment (AIS). Invertebrate neurons are typically unipolar with dendrites integrating directly into the axon. Where APs are initiated in the axons of invertebrate neurons is unclear. Voltage-gated sodium (NaV) channels are a functional hallmark of the AIS in vertebrates. We used an intronic MiMIC to determine the endogenous gene expression and subcellular localization of the sole NaV channel in both male and female Drosophila, para. Despite being the only NaV channel in the fly, we show that only 23 ±1% of neurons in the embryonic and larval CNS express para, while in the adult CNS para is broadly expressed. We generated a single-cell transcriptomic atlas of the whole 3rd instar larval brain to identify para expressing neurons and show that it positively correlates with markers of differentiated, actively firing neurons. Therefore only 23 ±1% of larval neurons may be capable of firing NaV-dependent APs. We then show that Para is enriched in an axonal segment, distal to the site of dendritic integration into the axon, which we named the Distal Axonal Segment (DAS). The DAS is present in multiple neuron classes in both the 3rd instar larval and adult CNS. Whole cell patch clamp electrophysiological recordings of adult CNS fly neurons are consistent with the interpretation that Nav-dependent APs originate in the DAS. Identification of the distal NaV localization in fly neurons will enable more accurate interpretation of electrophysiological recordings in invertebrates.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE157202 | GEO | 2020/09/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Analysis of NF186 proximity proteomes across neuronal development using Nfasc antibodies in an antibody-directed proximity biotinylation strategy combined with mass spectrometry

Project description:Axon initial segment (AIS) cell surface proteins mediate key biological processes in neurons including action potential initiation and axo-axonic synapse formation. However, few AIS cell surface proteins have been identified. Here, we used antibody-directed proximity biotinylation to define the cell surface proteins in close proximity to the AIS cell adhesion molecule Neurofascin.

2023-10-05 | PXD043805 | Pride

Immunoproximity biotinylation reveals the axon initial segment proteome

Project description:The axon initial segment (AIS) is a specialized neuronal compartment required for action potential generation and neuronal polarity. However, understanding the mechanisms regulating AIS structure and function has been hindered by an incomplete knowledge of its molecular composition. Here, using immuno-proximity biotinylation we further define the AIS proteome and its dynamic changes during neuronal maturation. Among the many AIS proteins identified, we show that SCRIB is highly enriched in the AIS both in vitro and in vivo, and exhibits a periodic architecture like the axonal spectrin-based cytoskeleton. We found that ankyrinG interacts with and recruits SCRIB to the AIS. However, loss of SCRIB has no effect on ankyrinG. This powerful and flexible approach further defines the AIS proteome and provides a rich resource to elucidate the mechanisms regulating AIS structure and function.

2024-01-02 | PXD045921 | Pride

Regeneration occurs in the CNS of CAST/Ei mice as a consequence of enhanced Activin signaling

Project description:We screened nine genetically diverse inbred mouse strains for differences in axonal growth of adult dorsal root ganglion (DRG) neurons on CNS myelin. Naïve DRG neurite outgrowth on myelin was very limited, but preconditioning the neurons by a prior sciatic nerve crush increased axonal growth substantially across all strains, with by far the greatest change in neurons from CAST/Ei mice. Three independent in vivo CNS injury models revealed greater capacity for CNS axonal regeneration in CAST/Ei than C57BL/6 mice. Full-genome expression profiling of naïve and pre-conditioned DRGs across all strains revealed Activin-βA (Inhba) as the transcript whose expression most closely correlated with axonal growth on myelin. In vitro and in vivo gain- and loss-of-function experiments confirmed that Activin promotes axonal growth in the CNS. Substantial regeneration is possible, therefore, in the injured mammalian CNS when Activin signaling is intrinsically high, as in CAST/Ei or when extrinsically modulated in other strains. 9 strains, 4 replicates per strain, 2 conditions (naïve and axotomy) = 72 samples. 2 samples were excluded because technical outliers (AJ_AX5D_1 and AJ_NAIVE_4 excluded from the normalized data but included in the raw data)

2015-05-14 | E-GEOD-55424 | biostudies-arrayexpress

Regeneration occurs in the CNS of CAST/Ei mice as a consequence of enhanced Activin signaling

2015-05-14 | GSE55424 | GEO

The Alk receptor tyrosine kinase regulates Sparkly, a novel activity regulating neuropeptide precursor in the Drosophila CNS

Project description:Numerous roles for the Alk receptor tyrosine kinase have been described in Drosophila, including functions in the CNS, however the molecular details are poorly understood. To gain mechanistic insight, we employed Targeted DamID (TaDa) transcriptional profiling to identify targets of Alk signaling in the larval CNS. TaDa was employed in larval CNS tissues, while genetically manipulating Alk signaling output. The resulting TaDa data were analysed together with larval CNS scRNA-seq datasets performed under similar conditions, identifying a role for Alk in the transcriptional regulation of neuroendocrine gene expression. Further integration with bulk/scRNA-seq and protein datasets from larval brains in which Alk signaling was manipulated, identified a previously uncharacterized Drosophila neuropeptide precursor encoded by CG4577 as an Alk signaling transcriptional target. CG4577, which we named Sparkly (Spar), is expressed in a subset of Alk-positive neuroendocrine cells in the developing larval CNS, including circadian clock neurons. In agreement with our TaDa analysis, overexpression of the Drosophila Alk ligand Jeb resulted in increased levels of Spar protein in the larval CNS. We show that Spar protein is expressed in circadian (Clock) neurons, and Spar mutants exhibit defects in sleep and circadian rhythm control. In summary, we report a novel activity regulating neuropeptide precursor gene that is regulated by Alk signaling in the Drosophila CNS.

2024-03-05 | GSE229518 | GEO

A chemical genetic approach identifies piperazine antipsychotics as promoters of CNS neurite growth on inhibitory substrates.

Project description:Injury to the central nervous system (CNS) may result in lifelong loss of function due, in part, to the regenerative failure of CNS neurons. Major barriers to regeneration faced by injured CNS neurons include inhibitory proteins derived from myelin and the astroglial scar. Previously, we described the identification of a novel compound, F05, which promotes neurite growth from neurons challenged with inhibitory substrates in vitro, and promotes axonal regeneration in vivo (Usher et al., 2010). To identify additional regeneration promoting compounds, we used the microarray derived gene expression signature of F05 to query the Broad Institute Connectivity Map, a database of gene expression profiles for cells treated with >1,300 compounds. Unexpectedly, F05 induced changes in gene expression remarkably similar to those seen with a group of piperazine phenothiazine antipsychotics (PhAPs). We found that, in contrast to antipsychotics of other structural classes, PhAPs were able to promote neurite growth of CNS neurons cultured on two different glial-derived inhibitory substrates, but did not promote growth on a permissive substrate. Pharmacological studies suggest that the ability of PhAPs to promote growth depends on antagonism of calmodulin signaling, but not on dopamine receptor antagonism. Our findings shed light on mechanisms underlying neurite-inhibitory signaling, and suggest a potential pathway for development of novel treatments for CNS injury. 3 Biological Replicates of Vehicle Treated (0.05% DMSO) + 3 Biological Replicates of F05 Treated (5 μM)

2012-04-29 | E-GEOD-34331 | biostudies-arrayexpress

Sphingolipid-dependent Dscam sorting regulates axon segregation

Project description:Neurons are highly polarized cells with distinct protein compositions in axonal and dendritic compartments. Cellular mechanisms controlling polarized protein sorting have been described for mature nervous system but little is known about the segregation in newly differentiated neurons. In a forward genetic screen for regulators of Drosophila brain circuit development, we identified mutations in <span style="color: rgb(54, 54, 54); font-style: normal; font-weight: 400; background-color: rgb(245, 245, 245);">Serine Palmitoyltransferase </span>(SPT), an evolutionary conserved enzyme in sphingolipid biosynthesis. Here we show that reduced levels of sphingolipids in SPT mutants cause axonal morphology defects similar to loss of cell recognition molecule Dscam. Loss- and gain-of-function studies show that neuronal sphingolipids are critical to prevent aggregation of axonal and dendritic Dscam isoforms, thereby ensuring precise Dscam localization to support axon branch segregation. Furthermore, SPT mutations causing neurodegenerative HSAN-I disorder in humans also result in formation of stable Dscam aggregates and axonal branch phenotypes in Drosophila neurons, indicating a causal link between developmental protein sorting defects and neuronal dysfunction.

2019-03-29 | MTBLS825 | MetaboLights

CTCF is required to form regulatory and physical boundaries at limited sites in the Drosophila nervous system [Hi-C]

Project description:CCCTC-binding factor (CTCF) is a conserved protein able to block communication between regulatory elements and gene promoters in flies and mammals. Here, we studied CTCF function in the Drosophila central nervous system (CNS) in which we find CTCF plays a vital role. Hi-C experiments on dissected larval CNSs of wildtype controls and CTCF[0] mutants that completely lack CTCF revealed that CTCF forms hundreds of physical boundaries in fly chromosomes.

2021-01-18 | GSE146750 | GEO

Drosophila CNS OXPHOS inhibition microarray

Project description:Mitochondrial dysfunction causes biophysical, metabolic and signalling changes that alter homeostasis and reprogram cells. We used a Drosophila model in which individual subunits of 4 OXPHOS complexes are knocked-down in neurons in the larval CNS. We used microarray analysis to investigate gene expression changes caused by knock down of OXPHOS subunits of complexes I, III, IV and V in neurons.

2017-03-21 | GSE96802 | GEO

Cell cycle-independent temporal identity transitions in cortical progenitor cells as revealed by single cell transcriptome analysis

Project description:During cerebral development, a variety of neurons are sequentially generated by self-renewing progenitor cells, apical progenitors (APs). A temporal change in AP identity is thought to produce a diversity of progeny neurons, while underlying mechanisms are largely unknown. Here we performed single cell genome-wide transcriptome profiling of APs at different neurogenic stages, and identified a set of genes that are temporally expressed in APs in a manner independent of differentiation state. Surprisingly, the temporal pattern of such AP gene expression was not affected by arresting cell cycling. Consistently, a transient cell cycle arrest of APs in vivo did not prevent descendant neurons to acquire their correct laminar fates. in vitro cell culture of APs revealed that transitions in AP gene expression involved in both cell-autonomous and non-autonomous mechanisms. These results suggest that timers controlling AP temporal identity run independently of cell cycle progression and Notch activation mode.　

2016-04-07 | GSE55981 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data