A High-Resolution Map Predicts Lineage and Birth Order Underlying Neuronal Identity
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ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE296540 | GEO | 2026/01/12
REPOSITORIES: GEO
Similar Datasets
Project description:A High-Resolution Map Predicts Lineage and Birth Order Underlying Neuronal Identity
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Project description:Spatially distributed sensory information is topographically mapped in the brain by point-to-point correspondence of connections between peripheral receptors and central target neurons. In fishes, for example, the axonal projections from the mechanosensory lateral line organize a somatotopic neural map. The lateral line provides hydrodynamic information for intricate behaviors such as navigation and prey detection. It also mediates fast startle reactions triggered by the Mauthner cell. However, it is not known how the lateralis neural map is built to subserve these contrasting behaviors. Here we reveal that birth order diversifies lateralis afferent neurons in the zebrafish. We demonstrate that early- and late-born lateralis afferents diverge along the main axes of the hindbrain to synapse with hundreds of second-order targets. However, early-born afferents projecting from primary neuromasts also assemble a separate map by converging on the lateral dendrite of the Mauthner cell, whereas projections from secondary neuromasts never make physical contact with the Mauthner cell. We also show that neuronal diversity and map topology occur normally in animals permanently deprived of mechanosensory activity. We conclude that neuronal birth order correlates with the assembly of neural submaps, whose combination is likely to govern appropriate behavioral reactions to the sensory context.
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Project description:Single-cell technologies are offering unparalleled insight into complex biology, revealing the behavior of rare cell populations that are masked in bulk population analyses. One current limitation of single-cell approaches is that lineage relationships are typically lost as a result of cell processing. We recently established a method, CellTagging, permitting the parallel capture of lineage information and cell identity via a combinatorial cell indexing approach. CellTagging integrates with high-throughput single-cell RNA sequencing, where sequential rounds of cell labeling enable the construction of multi-level lineage trees. Here, we provide a detailed protocol to (i) generate complex plasmid and lentivirus CellTag libraries for labeling of cells; (ii) sequentially CellTag cells over the course of a biological process; (iii) profile single-cell transcriptomes via high-throughput droplet-based platforms; and (iv) generate a CellTag expression matrix, followed by clone calling and lineage reconstruction. This lentiviral-labeling approach can be deployed in any organism or in vitro culture system that is amenable to viral transduction to simultaneously profile lineage and identity at single-cell resolution.
| S-EPMC7427510 | biostudies-literature
Project description:The brain exhibits remarkable neuronal diversity which is critical for its functional integrity. From the sheer number of cell types emerging from extensive transcriptional, morphological, and connectome datasets, the question arises of how the brain is capable of generating so many unique identities. 'Terminal selectors' are transcription factors hypothesized to determine the final identity characteristics in post-mitotic cells. Which transcription factors function as terminal selectors and the level of control they exert over different terminal characteristics are not well defined. Here, we establish a novel role for the transcription factor broad as a terminal selector in Drosophila melanogaster. We capitalize on existing large sequencing and connectomics datasets and employ a comprehensive characterization of terminal characteristics including Perturb-seq and whole-cell electrophysiology. We find a single isoform broad-z4 serves as the switch between the identity of two visual projection neurons LPLC1 and LPLC2. Broad-z4 is natively expressed in LPLC1, and is capable of transforming the transcriptome, morphology, and functional connectivity of LPLC2 cells into LPLC1 cells when perturbed. Our comprehensive work establishes a single isoform as the smallest unit underlying an identity switch, which may serve as a conserved strategy replicated across developmental programs.
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Project description:The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila.
| S-EPMC4846375 | biostudies-literature
Project description:Artists and astronomers noticed centuries ago that humans perceive dark features in an image differently from light ones; however, the neuronal mechanisms underlying these dark/light asymmetries remained unknown. Based on computational modeling of neuronal responses, we have previously proposed that such perceptual dark/light asymmetries originate from a luminance/response saturation within the ON retinal pathway. Consistent with this prediction, here we show that stimulus conditions that increase ON luminance/response saturation (e.g., dark backgrounds) or its effect on light stimuli (e.g., optical blur) impair the perceptual discrimination and salience of light targets more than dark targets in human vision. We also show that, in cat visual cortex, the magnitude of the ON luminance/response saturation remains relatively constant under a wide range of luminance conditions that are common indoors, and only shifts away from the lowest luminance contrasts under low mesopic light. Finally, we show that the ON luminance/response saturation affects visual salience mostly when the high spatial frequencies of the image are reduced by poor illumination or optical blur. Because both low luminance and optical blur are risk factors in myopia, our results suggest a possible neuronal mechanism linking myopia progression with the function of the ON visual pathway.
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Project description:Expression and alternative splicing data from 1-month-old Rbfox1 KO brain. Rbfox1 regulates the alternative splicing of many transcripts in neurons. We have characterized the Rbfox1-dependent changes in expression and alternative splicing by comparing Rbfox1-KO brain to WT brain. In this dataset, we include the splicing and expression data obtained from dissected WT and Rbfox1 KO mouse brains.
2011-05-16 | GSE28421 | GEO
Project description:An association between birth order and reduced unaided vision (a surrogate for myopia) has been observed previously. We examined the association between birth order and myopia directly in four subject groups.Subject groups were participants in (1) the Avon Longitudinal Study of Parents and Children (ALSPAC; UK; age 15 years; N = 4401), (2) the Singapore Cohort Study of Risk Factors for Myopia (SCORM; Singapore; age 13 years; N = 1959), (3) the Raine Eye Health Study (REHS; Australia; age 20 years; N = 1344), and (4) Israeli Defense Force Pre-recruitment Candidates (IDFC; Israel; age 16-22 years; N = 888,277). The main outcome was odds ratios (OR) for myopia in first-born versus non-first-born individuals after adjusting for potential risk factors.The prevalence of myopia was numerically higher in first-born versus non-first-born individuals in all study groups, but the strength of evidence varied widely. Adjusted ORs (95% confidence intervals, CIs) were: ALSPAC, 1.31 (1.05-1.64); SCORM, 1.25 (0.89-1.77); REHS, 1.18 (0.90-1.55); and IDFC, 1.04 (1.03-1.06). In the large IDFC sample, the effect size was greater (a) for the first-born versus fourth- or higher-born comparison than for the first-born versus second/third-born comparison (p < 0.001) and (b) with increasing myopia severity (p < 0.001).Across all studies, the increased risk of myopia in first-born individuals was low (OR < 1.3). Indeed, only the studies with >4000 participants provided strong statistical support for the association. The available evidence suggested the relationship was independent of established risk factors such as time outdoors/reading, and thus may arise through a different causal mechanism.
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Project description:Neuronal diversity is an intrinsic feature of the nervous system. Transcription factors (TFs) are key regulators in the establishment of different neuronal identities; how are the actions of different TFs coordinated to orchestrate this diversity? Are there common features shared among the different neuron types of an organism or even among different animal groups? In this review, we provide a brief overview on common traits emerging on the transcriptional regulation of neuron type diversification with a special focus on the comparison between mouse and Caenorhabditis elegans model systems. In the first part, we describe general concepts on neuronal identity and transcriptional regulation of gene expression. In the second part of the review, TFs are classified in different categories according to their key roles at specific steps along the protracted process of neuronal specification and differentiation. The same TF categories can be identified both in mammals and nematodes. Importantly, TFs are very pleiotropic: Depending on the neuron type or the time in development, the same TF can fulfil functions belonging to different categories. Finally, we describe the key role of transcriptional repression at all steps controlling neuronal diversity and propose that acquisition of neuronal identities could be considered a metastable process.
| S-EPMC9306894 | biostudies-literature
Project description:Transcriptional programs that regulate development are exquisitely controlled in space and time. Elucidating these programs that underlie development is essential to understanding the acquisition of cell and tissue identity. We present microarray expression profiles of a high resolution set of developmental time points within a single Arabidopsis root, and a comprehensive map of nearly all root cell-types. These cell-type specific transcriptional signatures often predict novel cellular functions. A computational pipeline identified dominant expression patterns that demonstrate transcriptional connections between disparate cell types. Dominant expression patterns along the root’s longitudinal axis do not strictly correlate with previously defined developmental zones, and in many cases, expression fluctuation along this axis was observed. Both robust co-regulation of gene expression and potential phasing of gene expression were identified between individual roots. Methods that combine these two sets of profiles demonstrate transcriptionally rich and complex programs that define Arabidopsis root development in both space and time. We used microarrays to profile expression of nearly all cell types in the Arabidopsis root, and to profile at high resolution, developmental time points along the root's longitudinal axis. Keywords: Cell-type specific analysis using FACS, and a developmental time course.
2007-11-05 | GSE8934 | GEO