Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1033781 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26589822.fastq.gz | Fastqsanger.gz | |||
| SRR26589823.fastq.gz | Fastqsanger.gz | |||
| SRR26589824.fastq.gz | Fastqsanger.gz | |||
| SRR26589825.fastq.gz | Fastqsanger.gz | |||
| SRR26589826.fastq.gz | Fastqsanger.gz |
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Project description:How our brain generates diverse neuron types that assemble into precise neural circuits remains unclear. Using Drosophila lamina neuron types (L1-L5), we show that the primary homeodomain transcription factor (HDTF) Brain-specific homeobox (Bsh) is initiated in progenitors and maintained in L4/L5 neurons to adulthood. Bsh activates secondary HDTFs Ap (L4) and Pdm3 (L5) and specifies L4/L5 neuronal fates while repressing the HDTF Zfh1 to prevent ectopic L1/L3 fates (control: L1-L5; Bsh-knockdown: L1-L3), thereby generating lamina neuronal diversity for normal visual sensitivity. Subsequently, in L4 neurons, Bsh and Ap function in a feed-forward loop to activate the synapse recognition molecule DIP-β, thereby bridging neuronal fate decision to synaptic connectivity. Expression of a Bsh:Dam specifically in L4 reveals Bsh binding to the DIP-β locus and additional candidate L4 functional identity genes. We propose that HDTFs function hierarchically to coordinate neuronal molecular identity, circuit formation, and function. Hierarchical HDTFs may represent a conserved mechanism for linking neuronal diversity to circuit assembly and function.
2023-11-05 | GSE246726 | GEO
Project description:The recognition of synaptic partners and specification of synaptic properties are fundamental for the function of neuronal circuits. 'Terminal selector' transcription factors coordinate the expression of terminal gene batteries that specify cell type-specific properties. Moreover, pan-neuronal alternative splicing regulators have been implicated in directing neuronal differentiation. However, the cellular logic of how splicing regulators instruct specific synaptic properties remains poorly understood. Here, we combine genome-wide mapping of mRNA targets and cell type-specific loss-of-function studies to uncover the contribution of the nuclear RNA binding protein SLM2 to hippocampal synapse specification. We find that SLM2 preferentially binds and regulates alternative splicing of transcripts encoding synaptic proteins, thereby generating cell type-specific isoforms. In the absence of SLM2, cell type-specification, differentiation, and viability are unaltered and neuronal populations exhibit normal intrinsic properties. By contrast, cell type-specific loss of SLM2 results in highly selective, non-cell autonomous synaptic phenotypes, altered synaptic transmission, and associated defects in a hippocampus-dependent memory task. Thus, alternative splicing provides a critical layer of gene regulation that instructs specification of neuronal connectivity in a trans-synaptic manner.
2022-12-08 | GSE220062 | GEO
Project description:Understanding neuronal connectivity at single-cell resolution remains a fundamental challenge in neuroscience, with current methods constrained by an inherent trade-off between throughput and synaptic precision. Here we present Connectome-seq, a high-throughput method that combines engineered synaptic proteins, RNA barcoding, and single-compartment sequencing to map neuronal connectivity at single-synapse resolution. We validate this approach in the mouse pontocerebellar circuit, successfully identifying thousands of connections including the predominant excitatory projections from pontine neurons to cerebellar granule cells, while also revealing potentially novel synaptic partnerships. By enabling systematic mapping of neuronal connectivity across brain regions with single-cell precision, Connectome-seq provides a scalable platform for comprehensive circuit analysis across different experimental conditions and biological states. This advance in connectivity mapping methodology opens new possibilities for understanding circuit organization in complex mammalian brains.
2025-12-16 | GSE312903 | GEO
Project description:Understanding neuronal connectivity at single-cell resolution remains a fundamental challenge in neuroscience, with current methods constrained by an inherent trade-off between throughput and synaptic precision. Here we present Connectome-seq, a high-throughput method that combines engineered synaptic proteins, RNA barcoding, and single-compartment sequencing to map neuronal connectivity at single-synapse resolution. We validate this approach in the mouse pontocerebellar circuit, successfully identifying thousands of connections including the predominant excitatory projections from pontine neurons to cerebellar granule cells, while also revealing potentially novel synaptic partnerships. By enabling systematic mapping of neuronal connectivity across brain regions with single-cell precision, Connectome-seq provides a scalable platform for comprehensive circuit analysis across different experimental conditions and biological states. This advance in connectivity mapping methodology opens new possibilities for understanding circuit organization in complex mammalian brains.
2025-12-31 | GSE285978 | GEO
Project description:Patterns of synaptic connectivity are remarkably precise and complex. Single-cell RNA sequencing has revealed a vast transcriptional diversity of neurons. Nevertheless, a clear logic underlying the transcriptional control of neuronal connectivity has yet to emerge. Here, we focused on Drosophila T4/T5 neurons, a class of closely related neuronal subtypes with different wiring patterns. Eight subtypes of T4/T5 neurons are defined by combinations of two patterns of dendritic inputs and four patterns of axonal outputs. Single-cell profiling during development revealed distinct transcriptional programs defining each dendrite and axon wiring pattern. These programs were defined by the expression of a few transcription factors and different combinations of cell surface proteins. Gain and loss of function studies provide evidence for independent control of different wiring features. We propose that modular transcriptional programs for distinct wiring features are assembled in different combinations to generate diverse patterns of neuronal connectivity.
2019-11-05 | GSE126139 | GEO
Project description:How neuronal connections are established and organized in functional networks determines brain function. In the mouse cerebral cortex, different classes of GABAergic interneurons exhibit specific connectivity patterns that underlie their ability to shape temporal dynamics and information processing. Much progress has been made parsing interneuron diversity, yet the molecular mechanisms by which interneuron subtype-specific connectivity motifs emerge remain unclear. Here we investigate transcriptional dynamics in different classes of interneurons during the formation of cortical inhibitory circuits. We found that whether the interneurons synapse with pyramidal neurons on their dendrites, soma, or axon initial segment is determined by synaptic molecules that are expressed in a subtype-specific manner. Thus cell-specific molecular programs that unfold during early postnatal development underlie the connectivity patterns of cortical interneurons.
2019-01-25 | GSE120161 | GEO
Project description:Purpose: Information processing in the brain relies on precise patterns of synapses between neurons. The molecular mechanisms by which this specificity is achieved remains elusive. In the medulla of the Drosophila visual system, different neurons form synaptic connections in different layers. Methods: we developed methods to purify seven neuronal cell types (R7, R8 and L1-L5 neurons) using Fluorescence Activated Cell Sorting. Results: we show that neurons with different synaptic specificities express unique combinations of mRNAs encoding hundreds of cell surface and secreted proteins. Using RNA sequencing and MiMIC-based protein tagging, we demonstrate that 21 paralogs of the Dpr family, a subclass of Immunoglobulin (Ig)-domain containing proteins, are expressed in unique combinations in homologous neurons with different layer-specific synaptic connections. Dpr interacting proteins (DIPs), comprising nine paralogs of another subclass of Ig superfamily proteins, are expressed in a complementary layer-specific fashion in a subset of synaptic partners. We propose that pairs of Dpr/DIP paralogs contribute to layer-specific patterns of synaptic connectivity. Conclusions: This complexity is mirrored by the complexity of the cell surface and secreted molecules expressed by each of the R cell and lamina neurons profiled in this study. How this complexity contributes to specificity remains elusive, but the convergence of improved histological, genetic and molecular tools promises to provide important insights into the molecular recognition strategies controlling synaptic specificity. We chose 7 time points for RNA-seq analysis of R cells during pupal development corresponding to 24, 35, 40, 45, 53, 65 and 96 hrs after pupal formation (APF).
2015-12-17 | E-GEOD-68235 | biostudies-arrayexpress
Project description:Cellular and animal models and human specimens are used to show that in Alzheimer's disease, neuronal changes are mediated through pathologic chaperome networks, referred to as epichaperomes, leading to alterations in neuronal protein-protein connectivity and function. Epichaperome inhibition in cellular and mouse models of AD results in rebalance of synaptic protein networks, recovery of hippocampal LTP synaptic plasticity and cognitive function to wild-type levels. Our study uncovers cognitive deficits in AD that stem from an inability to encode new information because of aberrant neuronal protein-protein interaction networks.
2019-02-25 | MSV000083484 | MassIVE
Project description:Activity-dependent gene expression is central for sculpting neuronal connectivity in the brain. Despite the importance for synaptic plasticity, a comprehensive analysis of the temporal changes in the transcriptomic response to neuronal activity is lacking. In a genome wide survey we identified genes that were induced at 1, 4, 8, or 24 hours following neuronal activity in the hippocampus. 3 month old male mice were injected with kainic acid or isotonic saline solution. Animals were sacrificed by cervical luxation 1, 2, 4, 8, or 24 h after onset of the first seizure, and RNA was extracted from the hippocampal region.
2013-10-23 | E-GEOD-49030 | biostudies-arrayexpress
Project description:How progenitor identity instructs neuronal diversification remains unclear. We uncover a homeodomain transcription factor (HDTF) cascade that links the identity of a single lamina progenitor type to the diversification of all five lamina neuron subtypes in the Drosophila visual system. Hedgehog signaling induces a pan-class HDTF—expressed across all subtypes of a neuronal class, here all lamina neurons—in progenitors, promoting cell-cycle exit. This progenitor-derived pan-class HDTF is inherited by newborn lamina neurons, where it activates subtype-specific, differentially expressed (DE) HDTFs and acts combinatorially with these DE-HDTFs to specify distinct neuronal subtypes. Loss of DE-HDTFs induces predictable, subtype-specific fate conversions—morphological and functional—reducing neuronal diversity. Strikingly, we find mouse retinal neurons express analogous pan-class and DE-HDTFs, indicating an evolutionarily conserved strategy. With HDTFs broadly expressed, our findings define a progenitor-to-newborn HDTF cascade that provides a generalizable mechanism by which progenitor identity drives neuronal diversification from a limited progenitor pool.
2025-08-25 | GSE305551 | GEO