Perinatal correlated retinal activity is required for the wiring of visual axons in non-image forming nuclei
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA796364 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17567851.fastq.gz | Fastqsanger.gz | |||
| SRR17567852.fastq.gz | Fastqsanger.gz | |||
| SRR17567853.fastq.gz | Fastqsanger.gz | |||
| SRR17567854.fastq.gz | Fastqsanger.gz | |||
| SRR17567855.fastq.gz | Fastqsanger.gz |
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Project description:The formation of the visual system is a complex multistep process that includes the establishment of proper connectivity of retinal ganglion cell (RGC) axon terminals with their relay neurons located in the brain. In mammals, the assembly of the different components of the visual circuit occurs at perinatal stages before eye opening. Upon reaching the target nuclei RGC axons extensively arborize and subsequently refine to establish the final connections. Spontaneous activity generated in the immature retina plays an essential role in the refinement of visual terminals at the main image-forming nuclei (IFN) that follow an eye-specific and retinotopic organization. However, the molecular mechanisms underlying spontaneous activity-dependent axon remodeling, and the influence of this activity in the connectivity of non-image forming nuclei (NIFN) that lack precise retinotopic maps and/or eye-specific segregation, are not well known. Here, by generating conditional mice with disturbed spontaneous retinal aneactivity and analyzing their retinal transcriptomic profiles, we identified novel players involved in axon refinement at the visual nuclei (e. g. Syt13). The analysis of visual projections in the NIFN of these mice revealed that correlated-retinal activity shapes final connectivity in non retinotopic or eye-specific segregating visual nuclei.
2024-10-09 | GSE193498 | GEO
Project description:Local mRNA translation mediates the adaptive responses of axons to extrinsic signals but direct evidence that it occurs in mammalian CNS axons in vivo is scant. We developed an axon-TRAP-RiboTag approach in mouse that allows deep-sequencing analysis of ribosome-bound mRNAs in the retinal ganglion cell axons of the developing and adult retinotectal projection in vivo. The embryonic-to-postnatal axonal translatome comprises an evolving subset of enriched genes with axon-specific roles suggesting distinct steps in axon wiring, such as elongation, pruning and synaptogenesis. Adult axons, remarkably, have a complex translatome with strong links to axon survival, neurotransmission and neurodegenerative disease. Translationally co-regulated mRNA subsets share common upstream regulators, and novel sequence elements generated by alternative splicing that promote axonal mRNA translation. Our results indicate that intricate regulation of compartment-specific mRNA translation in mammalian CNS axons supports the formation and maintenance of neural circuits in vivo. The profiling of ribosome-bound mRNAs in mouse retinal ganglion cell axons at 4 different developmental stages
2016-06-16 | E-GEOD-79352 | biostudies-arrayexpress
Project description:Local mRNA translation mediates the adaptive responses of axons to extrinsic signals but direct evidence that it occurs in mammalian CNS axons in vivo is scant. We developed an axon-TRAP-RiboTag approach in mouse that allows deep-sequencing analysis of ribosome-bound mRNAs in the retinal ganglion cell axons of the developing and adult retinotectal projection in vivo. The embryonic-to-postnatal axonal translatome comprises an evolving subset of enriched genes with axon-specific roles suggesting distinct steps in axon wiring, such as elongation, pruning and synaptogenesis. Adult axons, remarkably, have a complex translatome with strong links to axon survival, neurotransmission and neurodegenerative disease. Translationally co-regulated mRNA subsets share common upstream regulators, and novel sequence elements generated by alternative splicing that promote axonal mRNA translation. Our results indicate that intricate regulation of compartment-specific mRNA translation in mammalian CNS axons supports the formation and maintenance of neural circuits in vivo.
2016-06-16 | GSE79352 | GEO
Project description:Brain development is orchestrated by both innate and experience-dependent mechanisms, but their relative contributions are often difficult to resolve. Here we asked if and how central visual areas are altered in a vertebrate brain depleted of any and all signals from retinal ganglion cells throughout development. We transcriptionally profiled neurons in pretectum, thalamus and other retinorecipient areas of larval zebrafish and searched for changes in lakritz mutants that lack all retinal connections. Although individual genes are dysregulated, the complete set of 77 neuronal types develops in apparently normal proportions, at normal locations, and along normal differentiation trajectories. Strikingly, the cell-cycle exits of proliferating progenitors in these areas are delayed, and a greater fraction of early postmitotic precursors remain uncommitted or are diverted to a glial fate. Optogenetic stimulation targeting groups of neurons normally involved in processing visual information evokes behaviors indistinguishable from wildtype. In conclusion, we show that signals emitted by retinal axons influence the pace of neurogenesis in visual areas, but do not detectably affect the specification or wiring of downstream neurons.
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Project description:Loss-of-function mutations in chromatin remodeler gene ARID1A are a cause of Coffin-Siris syndrome, a developmental disorder characterized by dysgenesis of corpus callosum. Here, we characterize Arid1a function during cortical development and find unexpectedly selective roles for Arid1a in subplate neurons. Subplate neurons (SPNs), strategically positioned at the interface of cortical grey and white matter, orchestrate multiple developmental processes indispensable for neural circuit wiring. We find that pan-cortical deletion of Arid1a leads to extensive mistargeting of intracortical axons and agenesis of corpus callosum. Sparse Arid1a deletion, however, does not autonomously misroute callosal axons, implicating non-cell autonomous Arid1a functions in axon guidance. Supporting this possibility, the ascending axons of thalamocortical neurons, which are not autonomously affected by cortical Arid1a deletion, are also disrupted in their pathfinding into cortex and innervation of whisker barrels. Coincident with these miswiring phenotypes, which are reminiscent of subplate ablation, we unbiasedly find a selective loss of SPN gene expression following Arid1a deletion. In addition, multiple characteristics of SPNs crucial to their wiring functions, including subplate organization, subplate-thalamocortical axon co-fasciculation (“handshake”), and extracellular matrix, are severely disrupted. To empirically test Arid1a sufficiency in subplate, we generate a cortical plate deletion of Arid1a that spares SPNs. In this model, subplate Arid1a expression is sufficient for subplate-thalamocortical axon co-fasciculation and extracellular matrix assembly. Consistent with these wiring functions, subplate Arid1a sufficiently enables normal callosum formation, thalamocortical axon targeting, and whisker barrel development. Thus, Arid1a is a multifunctional regulator of subplate-dependent guidance mechanisms essential to cortical circuit wiring.
2021-05-06 | GSE163273 | GEO
Project description:Although evidence indicates that the adult brain retains a considerable capacity for circuit formation, adult wiring has not been broadly considered and remains poorly understood. Here, we investigated wiring activation in adult neurons. Based on bioinformatic analyses on a previously published dataset (GSE161619), we identified the basic-helix-loop-helix (bHLH) transcription factor Ascl4 as a potential regulator of adult wiring and show that the AAV-mediated overexpression of Ascl4 can cell autonomously induce wiring in different types of hippocampal neurons of adult mice. The new axons are mainly feedforward and reconfigure synaptic weights in the hippocampal circuit. Mice with rewired circuits do not display signs of pathology and solve spatial problems equally well as controls. Our results demonstrate reprogrammed connectivity by a single transcriptional factor and provide insights into the regulation of brain connectivity in adults.
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Project description:The assembly of neural circuits is dependent upon precise spatiotemporal expression of cell recognition molecules1–6. Factors controlling cell-type specificity have been identified7–9, but how timing is determined remains unknown. Here we describe the induction of a cascade of transcription factors by a steroid hormone (Ecdysone) in all fly visual system neurons spanning target recognition and synaptogenesis. We demonstrate through single cell sequencing that the Ecdysone pathway regulates the expression of a common set of targets required for synaptic maturation and cell-type specific targets enriched for cell surface proteins regulating wiring specificity. Transcription factors in the cascade regulate the expression of the same wiring genes in complex ways, including activation in one cell-type and repression in another. We show that disruption of the Ecdysone-pathway generates specific defects in dendritic and axonal processes and synaptic connectivity, with the order of transcription factor expression correlating with sequential steps in wiring. We also identify shared targets of a cell-type specific transcription factor and the Ecdysone pathway which regulate specificity. We propose neurons integrate a global temporal transcriptional module with cell-type specific transcription factors to generate different cell-type specific patterns of cell recognition molecules regulating wiring.
2021-12-14 | GSE190714 | GEO
Project description:The mechanisms controlling wiring of neuronal networks are not completely understood. The stereotypic architecture of the Drosophila mushroom-body (MB) offers a unique system to study circuit assembly. The adult medial MB γ-lobe is comprised of a long bundle of axons that wires with specific modulatory and output neurons in a tiled manner defining five distinct zones. We found that the immunoglobulin superfamily protein Dpr12 is cell-autonomously required in γ-neurons for their developmental regrowth into the distal γ4/5 zones, where both Dpr12 and its interacting protein, DIP-δ, are enriched. DIP-δ functions in a subset of dopaminergic neurons that wire with γ-neurons within the γ4/5 zone. During metamorphosis, these dopaminergic projections arrive to the γ4/5 zone prior to γ-axons, suggesting that γ-axons extend through a prepatterned region. Thus, Dpr12/DIP-δ transneuronal interaction is required for γ4/5 zone formation. Our study sheds light onto molecular and cellular mechanisms underlying circuit formation within subcellular resolution.
2021-04-13 | GSE165896 | GEO
Project description:Mature cortical sensory areas are specialized to process unique sensory stimuli. Recent evidence shows that in the mouse embryo sensory cortices are prepared to respond to an incoming input from the periphery. However, whether these sensory circuits originate as modality specific modules, or they are segregated over time remains unknown. Here, we demonstrate that visual and somatosensory circuits originate as functionally intermingled modules, as whisker-pad stimulations at prenatal life led to a multimodal response activating both primary visual and somatosensory cortices. This multimodal response is switched to unimodal at birth via the superior colliculus, a midbrain structure where both modalities converge. Retinal afferent to the superior colliculus prompts the gating of visual from somatosensory circuits achieving sensory modality specificity at birth. Blocking stage I retinal waves resulted in prolonged convergence of somatosensory and visual circuits at the superior colliculus, which led to long-term consequences in the molecular identity of the superior colliculus and caused defects in eye-specific segregation and retinotopy. Hence, the superior colliculus stands as a key developmental regulator of sensory circuits by channeling modality stimuli to their appropriate sensory pathway.
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Project description:Local protein synthesis is rapidly regulated by extrinsic signals during neural wiring but the translational control mechanisms remain elusive. Here, we show that the guidance cue Sema3A, but not Slit1, elicits precise spatiotemporal control of the phosphorylation of the translation initiation factor, eIF2α, in axonal growth cones via the Unfolded Protein Response (UPR) kinase PERK. Strikingly, in contrast to the canonical UPR signaling, we find that the Sema3A-induced eIF2α phosphorylation bypasses the conventional global translational repression and underlies a burst in axonal protein synthesis, mediated by differential eIF2B activity. Ultrasensitive proteomics on somaless axons reveals a subset of 75 proteins translationally regulated via Sema3A-p-eIF2α, including several proteostasis- and actin cytoskeleton-related nascent proteins. Finally, in vivo experiments provide evidence that eIF2α phosphorylation drives the formation of the retinotectal axon projection. Thus, specific extracellular cues can trigger non-canonical PERK-eIF2α-eIF2B signaling leading to subcellular dynamic remodeling of the nascent proteome required for neural wiring.
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