Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulation of brain development by subcommissural organ-derived peptides Tβ4,Tβ10, and NP24

ABSTRACT: The subcommissural organ (SCO) is an ancient and evolutionarily conserved gland in the brain located at the entrance of the aqueduct of Sylvius. It exists in species as distantly related as amphioxus and humans, but the function of the SCO is still mysterious. Comparison of transcriptomes between SCO and non-SCO brain regions revealed three unique genes, namely Sspo, Car3, and Spdef, that are highly enriched in the SCO. We generated the corresponding gene knock-in mouse strains utilizing the Cre/lox recombinase system for specific expression in SCO cells. Genetic ablation of SCO cells at embryonic stages with these strains revealed that SCO excision resulted in severe hydrocephalus and developmental defects in the brain. Abnormalities were also observed for neuronal migration and axon and dendrite development in the cerebral cortex. Taking advantage of non-targeted peptidomic analysis, we identified three SCO-derived peptides, namely thymosin beta 4 (Tβ4), thymosin beta 10 (Tβ10), and NP24. We found that these SCO peptides contributed to neurite development and neuronal survival in vitro. Indeed, application of a cocktail containing Tβ4, Tβ10 and NP24 to SCO-ablated brain ventricles substantially rescued their developmental defects. Our results demonstrate that SCO-derived peptides play critical roles in neuronal development.

ORGANISM(S): Mus Musculus

SUBMITTER: Wooping Ge

PROVIDER: PXD046221 | iProX | Wed Oct 18 00:00:00 BST 2023

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Similar Datasets

Neuronal membrane proteasome-derived peptides modulate neuronal signaling

Project description:Neuronal membrane proteasome-derived peptides modulate neuronal signaling

| PRJNA944718 | ENA

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

Subcommissural organ (SCO) contributes to brain development via SCO-secreted peptides.

Project description:To explore the mechanism of SCO-derived peptides, we performed RNAseq in cultured neurons added with SCO peptide and control neurons which added with DPBS to identify the expression of some unique genes and possible pathway related to the function of SCO derived peptides. We cofirmed the role of SCO derived peptide which contribute in neuronal development,especially projection developent and cell survival. development and neuronal survival .

2024-11-30 | GSE226349 | GEO

ITGAV variants are associated with immune dysregulation, brain abnormalities, and very early onset Inflammatory Bowel Disease

Project description:Integrin alpha–V (ITGAV) forms heterodimers with beta subunits to regulate several cellular processes including transforming growth factor β (TGF-β) signaling. We examined three unrelated families with common disease features including two children born with congenital brain anomalies and later development of immune dysregulation, atopy, and colitis, and three fetuses with brain and developmental defects. Using whole exome and RNA sequencing and functional studies, we demonstrate that biallelic ITGAV variants caused abnormal splicing or mislocalized protein that led to dysregulated TGF-β signaling in these families. Furthermore, knockout itgav (-/-) zebrafish embryos developed brain defects with loss of microglia and juvenile itgav (-/-) zebrafish developed colitis. Together, we show the critical role of ITGAV in immune regulation and gut and brain homeostasis and disease pathogenesis.

2024-09-30 | GSE248975 | GEO

Modulation of gene expression by complement protein C1q in amyloid-beta injured neurons

Project description:Complement protein C1q is induced after injury in the brain and during Alzheimer's disease and has been shown to protect against amyloid-beta induced neuronal death. In this study, we used microarray approach to identify the pathways modulated by C1q that are associated with neuroprotection. Immature rat cortical primary neurons are treated with fibrillar amyloid-beta peptides and/or C1q for 3h before RNA extraction and hybridization on rat Affymetrix microarrays. Supplementary file: Processed/normalized, probe-level signal intensities from neurons treated with amyloid-beta or C1q. Median signal intensity used as global normalization method, done with JMP genomics (v5.0) software.

2012-12-21 | E-GEOD-28886 | biostudies-arrayexpress

Transcriptional networks identify synaptotagmin-like 3 as a regulator of cortical neuronal migration during early neurodevelopment

Project description:Human brain development is a complex process involving neural proliferation, differentiation, and migration which are directed by many essential cellular factors and drivers. Here, using the NetBID2 algorithm and developing human brain RNA sequencing(RNA-Seq) dataset, we identified synaptotagmin-like 3(SYTL3) as one of the top drivers of early human brain development. Interestingly, SYTL3 exhibited high activity but low expression in both early developmental human cortex and human embryonic stem cell(hESC)-derived neurons. Knockout of SYTL3(SYTL3 -KO) in human neurons or knockdown of Sytl3 in embryonic mouse cortex markedly promoted neuronal migration. Besides, SYTL3-KO caused an abnormal distribution of deep-layer neurons in brain organoids and reduced presynaptic neurotransmitter release in hESC-derived neurons. We further demonstrated that SYTL3-KO- accelerated neuronal migration was modulated by high expression of matrix metalloproteinases. Together, based on bioinformatics and biological experiments, we identified SYTL3 as a novel regulator of cortical neuronal migration in human and mouse developing brains.

2021-02-07 | E-MTAB-10058 | biostudies-arrayexpress

Mus musculus

Project description:Global developmental gene expression and pathway analysis of normal brain development and mouse models of human neuronal migration defects

| PRJNA152639 | ENA

Wild type vs. Nova2 KO mouse E14.5 cortex RNA

Project description:To assess the requirement of Nova2 for alternative processing of RNA in the developping brain. Neuronal migration leads to a highly organized laminar structure in the mammalian brain and its mis-regulation causes lissencephaly, behavioral and cognitive defects. Reelin signaling, mediated in part by a key adaptor, disabled-1 (Dab1), plays a critical but incompletely understood role in this process. We found that the neuron-specific RNA binding protein Nova2 regulates neuronal migration in late-generated cortical and Purkinje neurons. An unbiased HITS-CLIP and exon junction array search for Nova-dependent RNAs at E14.5 focused on components of the reelin pathway revealed only one candidate—an alternatively spliced isoform of Dab1 (Dab1.7bc). In utero electroporation demonstrated that Dab1.7bc was sufficient to induce neuronal migration defects in wild-type mice and exacerbate defects when Dab1 levels were reduced, while Dab1 overexpression mitigates defects in Nova2-null mice. Thus Nova2 regulates an RNA switch controlling the ability of Dab1 to mediate neuronal responsiveness to reelin signaling and neuronal migration, suggesting new links between splicing regulation, brain disease and development. Keywords: Comparative analysis RNA from the cortex of 3 wild type and 3 Nova2 KO E14.5 cortex. One array per biological replicate.

2010-07-07 | E-GEOD-22758 | biostudies-arrayexpress

Ciliogenesis defects after neurulation impact brain development and neuronal activity in larval zebrafish

Project description:Ciliogenesis defects after neurulation impact brain development and neuronal activity in larval zebrafish

| PRJNA1021586 | ENA

Comparing Control and Schizophrenic hiPSC-derived NPCs

Project description:Cell-based models of many neurological and psychiatric diseases, established by reprogramming patient somatic cells into human induced pluripotent stem cells (hiPSCs), have now been reported. While numerous reports have demonstrated that neuronal cells differentiated from hiPSCs are electrophysiologically active mature neurons, the “age” of these cells relative to cells in the human brain remains unresolved. Comparisons of gene expression profiles of hiPSC-derived neural progenitor cells (NPCs) and neurons to the Allen BrainSpan Atlas indicate that hiPSC neural cells most resemble first trimester neural tissue. Consequently, we posit that hiPSC-derived neural cells may most accurately be used to model the early developmental defects that contribute to disease predisposition rather than the late features of the disease. Though the characteristic symptoms of schizophrenia (SCZD) generally appear late in adolescence, it is now thought to be a neurodevelopmental condition, often predated by a prodromal period that can appear in early childhood. Postmortem studies of SCZD brain tissue typically describe defects in mature neurons, such as reduced neuronal size and spine density in the prefrontal cortex and hippocampus, but abnormalities of neuronal organization, particularly in the cortex, have also been reported. We postulated that defects in cortical organization in SCZD might result from abnormal migration of neural cells. To test this hypothesis, we directly reprogrammed fibroblasts from SCZD patients into hiPSCs and subsequently differentiated these disorder-specific hiPSCs into NPCs. SCZD hiPSC differentiated into forebrain NPCs have altered expression of a number of cellular adhesion genes, reduced WNT signaling and aberrant cellular migration. 3 independent differentiations (biological replicates) for each of four control and four schizophrenic patients were analyzed.

2014-04-01 | E-GEOD-40102 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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