Modular transcriptional programs separately define axon and dendrite connectivity
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA521120 | ENA |
REPOSITORIES: ENA
Similar Datasets
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: Not available
| S-EPMC6855804 | biostudies-literature
Project description:Transcription factors specify the fate and connectivity of developing neurons. We investigate how a lineage-specific transcription factor, Acj6, controls the precise dendrite targeting of Drosophila olfactory projection neurons (PNs) by regulating the expression of cell-surface proteins. Quantitative cell-surface proteomic profiling of wild-type and acj6 mutant PNs in intact developing brains and a proteome-informed genetic screen identified PN surface proteins that execute Acj6-regulated wiring decisions. These include canonical cell adhesion molecules and proteins previously not associated with wiring, such as Piezo, whose mechanosensitive ion channel activity is dispensable for its function in PN dendrite targeting. Comprehensive genetic analyses revealed that Acj6 employs unique sets of cell-surface proteins in different PN types for dendrite targeting. Combinatorial expression of Acj6 wiring executors rescued acj6 mutant phenotypes with higher efficacy and breadth than expression of individual executors. Thus, Acj6 controls wiring specificity of different neuron types by specifying distinct combinatorial expression of cell-surface executors.
2022-04-21 | GSE200841 | GEO
Project description: Not available
| S-EPMC5066264 | biostudies-literature
Project description:Neurons must function for decades of life but how these non-dividing cells are preserved is poorly understood. Using mouse serotonin (5-HT) neurons as a model, we discovered a novel adult-stage transcriptional program specialized to ensure the preservation of serotonergic connectivity. We uncover a switch in Lmx1b and Pet1 transcription factor function from controlling embryonic axonal growth to sustaining a transcriptomic signature of serotonergic connectivity comprising functionally diverse synaptic and axonal genes. Adult-stage deficiency of Lmx1b and Pet1 caused slowly progressive degeneration of 5-HT synapses and axons, increased susceptibility of 5-HT axons to neurotoxic injury, and abnormal stress responses. Axon degeneration occurred in a die back pattern and was accompanied by accumulation of alpha-synuclein and APP in spheroids and mitochondrial fragmentation without cell body loss. Our findings suggest neuronal connectivity is transcriptionally protected by maintenance of connectivity transcriptomes; progressive decay of such transcriptomes may contribute to age-related diseases of brain circuitry.
2022-03-24 | GSE189052 | GEO
Project description:Xie Q, Li J1, Li H, Udeshi ND, Svinkina T, Kohani S, Guajardo R, Mani DR, Xu C, Li T, Han S, Wei W, Shuster SA, Luginbuhl DJ, Ting AY, Carr SA, Luo L. 2022.
Transcription factors specify the fate and connectivity of developing neurons. To understand how distal neurites execute commands from these nucleus-residing factors to specify their connectivity, we investigated how a lineage-specific transcription factor, Acj6, controls the precise dendrite targeting of Drosophila olfactory projection neurons (PNs). Quantitative cell-surface proteomic profiling of wild-type and acj6 mutant PNs in intact developing brains and a proteome-informed genetic screen identified PN surface proteins that execute Acj6-regulated wiring decisions. These include canonical cell adhesion molecules and molecules previously not associated with wiring, such as the mechanosensitive ion channel Piezo. Ion channel activity is dispensable for Piezo's function in PN dendrite targeting. Combinatorial expression of Acj6 executors more strongly rescued specific acj6 mutant phenotypes than expression of individual executors. Together, our findings reveal that a key transcription factor controls wiring specificity of different neuron types by regulating expression of unique combinations of cell-surface executors.
2022-04-01 | MSV000089187 | MassIVE
Project description:An animal’s skin provides a first point of contact with the sensory environment, including noxious cues that elicit protective behavioral responses. Nociceptive somatosensory neurons densely innervate and intimately interact with epidermal cells to receive these cues, however the mechanisms by which epidermal interactions shape processing of noxious inputs is still poorly understood. Here, we identify a role for dendrite intercalation between epidermal cells in tuning sensitivity of Drosophila larvae to noxious mechanical stimuli. In wild-type larvae, dendrites of nociceptive class IV da neurons intercalate between epidermal cells at apodemes, which function as body wall muscle attachment sites, but not at other sites in the epidermis. From a genetic screen we identified miR-14 as a regulator of dendrite positioning in the epidermis: miR-14 is expressed broadly in the epidermis but not in apodemes, and miR-14 inactivation leads to excessive apical dendrite intercalation between epidermal cells. We found that miR-14 regulates expression and distribution of the epidermal Innexins ogre and Inx2 and that these epidermal gap junction proteins restrict epidermal dendrite intercalation. Finally, we found that altering the extent of epidermal dendrite intercalation had corresponding effects on nociception: increasing epidermal intercalation sensitized larvae to noxious mechanical inputs and increased mechanically evoked calcium responses in nociceptive neurons, whereas reducing epidermal dendrite intercalation had the opposite effects. Altogether, these studies identify epidermal dendrite intercalation as a mechanism for mechanical coupling of nociceptive neurons to the epidermis, with nociceptive sensitivity tuned by the extent of intercalation.
2024-03-31 | GSE262604 | GEO
Project description:Axon degeneration sculpts precise patterns of connectivity in the developing nervous system and is an early pathological hallmark of several adult-onset neurodegenerative disorders. Substantial progress has been made in identifying effector mechanisms that drive axon fragmentation, but far less is known about the upstream signaling pathways that initiate this process. Here we describe a role for the newly discovered axonal Membrane-associated Periodic Skeleton (MPS) –a quasi-1D periodic ultrastructure composed of actin, spectrin and associated molecules– during sensory axon degeneration. We find that trophic deprivation (TD) of sensory axons causes a rapid breakdown in the periodicity of the MPS in distal axons. These structural changes occur prior to and independently of caspase-driven axon fragmentation. We further show that acute actin destabilization to break down the MPS can initiate TD-related retrograde signaling. Actin stabilization prevents MPS breakdown during TD and blocks this signal. Moreover, deletion of βII-spectrin (Sptbn1), an obligate component of the MPS, suppresses this retrograde signaling and protects axons against degeneration. Together our data suggest that ultrastructural plasticity of the MPS underlies the earliest steps of axon degeneration.
2019-03-14 | PXD009854 | Pride
Project description:Truncating CHD8 mutations are amongst the highest confidence risk factors for autism spectrum disorders (ASD) identified to date. Here, we report that Chd8 heterozygous mice display increased brain size, motor delay, hypertelorism, pronounced hypoactivity, and anomalous responses to social stimuli. Whereas gene expression in the neocortex is only mildly affected at mid gestation, over 600 genes are differentially expressed in the early postnatal neocortex. Genes involved in cell adhesion and axon guidance are particularly prominent amongst the downregulated transcripts. Resting-state functional MRI identified increased synchronized activity in corticohippocampal and auditory-parietal networks in Chd8 heterozygous mutant mice, implicating altered connectivity as a potential mechanism underlying the behavioral phenotypes. Together, these data suggest that altered brain growth and diminished expression of important neurodevelopmental genes that regulate long-range brain wiring are followed by distinctive anomalies in functional brain connectivity in Chd8 +/− mice. Human imaging studies have reported altered functional connectivity in ASD patients, with long-range under-connectivity seemingly more frequent. Our data suggest that CHD8 haploinsufficiency represents a specific subtype of ASD where neuropsychiatric symptoms are underpinned by long-range over-connectivity.
2018-04-24 | GSE81103 | GEO
Project description:To analyze axon transcriptome of dentate gyrus granule cells, dorsal root ganglion cells and retinal ganglion cells, we perfomed axon RNA sequencing.Neurons were cultured in microfluidic chambers and axons were isolated. Total RNA of axons was collected separately and subjected to library construction using M01440v2 NuGEN Trio RNA-seq kit. After sequencencing,we used TPM method to normalize RNA-seq reads.
2024-02-26 | GSE201547 | GEO