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Transneuronal Dpr12/DIP-δ interactions facilitate compartmentalized dopaminergic innervation of Drosophila mushroom body axons

ABSTRACT: 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.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE165896 | GEO | 2021/04/13

REPOSITORIES: GEO

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Transneuronal Dpr12/DIP-δ interactions facilitate compartmentalized dopaminergic innervation of Drosophila mushroom body axons

Project description:Transneuronal Dpr12/DIP-δ interactions facilitate compartmentalized dopaminergic innervation of Drosophila mushroom body axons

| PRJNA698553 | ENA

Myelin plasticity in ventral tegmental area is required for opioid reward

Project description:All drugs of abuse induce long-lasting changes in synaptic transmission and neural circuit function that underlie substance use disorders. Another recently appreciated mechanism of neural circuit plasticity is mediated through activity-regulated changes in myelin that can tune circuit function and influence cognitive behavior1. Here, we explored the role of myelin plasticity in dopaminergic circuity and reward learning. We demonstrate that dopaminergic neuronal activity-regulated myelin plasticity is a key modulator of dopaminergic circuit function and opioid reward. Oligodendroglial lineage cells respond to dopaminergic neuronal activity evoked by either optogenetic stimulation of dopaminergic neurons, optogenetic inhibition of GABAergic neurons, or administration of morphine or cocaine. These oligodendroglial changes are evident selectively within the ventral tegmental area (VTA), but not along the axonal projections in the medial forebrain bundle nor within the target nucleus accumbens (NAc). Genetic blockade of oligodendrogenesis dampens dopamine release dynamics in nucleus accumbens and impairs behavioral conditioning to morphine. Taken together, these findings underscore a critical role for oligodendrogenesis in reward learning and identify dopaminergic neuronal activity-regulated myelin plasticity as an important circuit modification that is required for opioid reward.

2024-02-10 | GSE255072 | GEO

Neural connectivity molecules best identify the heterogeneous clock and dopaminergic cell types in the Drosophila adult brain

Project description:Our recent single-cell sequencing of most adult Drosophila circadian neurons indicated notable and unexpected heterogeneity. To address whether other populations are similar, we sequenced a large subset of adult brain dopaminergic neurons. Their gene expression heterogeneity is similar to that of clock neurons, i.e., both populations have two to three cells per neuron group. There was also unexpected cell-specific expression of neuron communication molecule messenger RNAs: G protein–coupled receptor or cell surface molecule (CSM) transcripts alone can define adult brain dopaminergic and circadian neuron cell type. Moreover, the adult expression of the CSM DIP-beta in a small group of clock neurons is important for sleep. We suggest that the common features of circadian and dopaminergic neurons are general, essential for neuronal identity and connectivity of the adult brain, and that these features underlie the complex behavioral repertoire of Drosophila.

2023-02-25 | GSE198948 | GEO

Gene expression of growth plate of mouse.

Project description:The growth plate is histomorphologically classified into four zones {resting zone (RZ), proliferating zone (PZ), maturing zone (MZ) and hypertrophic zone (HZ)}. Gene expression profile analyses of 4 zones were performed using microarrays.

2008-12-23 | GSE14007 | GEO

Conserved and cell type-specific transcriptional responses to IFN-γ in the ventral midbrain

Project description:Dysregulated inflammation within the central nervous system (CNS) contributes to neuropathology in infectious, autoimmune, and neurodegenerative disease. With the exception of microglia, major histocompatibility complex (MHC) proteins are virtually undetectable in the mature, healthy central nervous system (CNS). Neurons have generally been considered incapable of antigen presentation, and although interferon gamma (IFN-γ) can elicit neuronal MHC class I (MHC-I) expression and antigen presentation in vitro, it remains unclear whether similar responses occur in vivo. Here we directly injected IFN-γ into the ventral midbrain of mature mice and analyzed gene expression profiles of specific CNS cell types. We find that IFN-γ induces cellular proliferation and expression of MHC-II and associated genes only in microglia. However, IFN-γ upregulated MHC-I and associated mRNAs in ventral midbrain microglia, astrocytes, oligodendrocytes, and GABAergic, glutamatergic, and dopaminergic neurons. The core set of IFN-γ-induced genes and their response kinetics were conserved across neurons and glia, with a lower amplitude of expression in neurons. A diverse repertoire of genes was upregulated in glia, particularly microglia, while no neuron-specific responses to IFN-γ were observed. Using mutant mice to selectively delete the IFN-γ-binding domain of IFNGR1 in dopaminergic neurons, we demonstrate that dopaminergic neurons respond directly to IFN-γ. Our results suggest that most neurons are capable of responding directly to IFN-γ and upregulating MHC-I and related genes in vivo, but their expression amplitude and repertoire is limited compared to oligodendrocytes, astrocytes, and microglia.

2022-12-10 | GSE218132 | GEO

Investigation of Drosophila fruitless neurons that express Dpr/DIP cell adhesion molecules

Project description:Drosophila reproductive behaviors are directed by fruitless neurons. A reanalysis of genomic studies shows that genes encoding dpr and DIP Immunoglobulin superfamily (IgSF) members are expressed in fru P1 neurons. We find that each fru P1 and dpr/DIP (fru P1 ∩ dpr/DIP) overlapping expression pattern is similar in both sexes, but there are dimorphisms in neuronal morphology and cell number. Behavioral studies of fru P1 ∩ dpr/DIP perturbation genotypes indicates that the mushroom body functions together with the lateral protocerebral complex to direct courtship behavior. A single-cell RNA-seq analysis of fru P1 neurons shows that many DIPs have high expression in a small set of neurons, whereas the dprs are often expressed in a larger set of neurons at intermediate levels, with a myriad of dpr/DIP expression combinations. Functionally, we find that perturbations of sex hierarchy genes and of DIP-ε change the sex-specific morphologies of fru P1 ∩ DIP-α neurons.

2021-02-23 | GSE162098 | GEO

Mushroom body cell type comparison

Project description:The Drosophila melanogaster mushroom bodies (MBs) are brain structures critical for olfactory memory. The approximately 2000 intrinsic MB neurons are divisible into alpha/beta neurons, alpha'/beta' neurons and gamma neurons by morphology and roles in memory processing. It has also been shown that the different subtypes of MB neurons have different function in the process of memory formation. This difference in function, suggested to us that different types of MB neurons might have different expression profiles. In this study, we used cell-type specific gene expression profiling to gain insight into cellular properties of MB neurons.

2013-01-10 | E-MEXP-3798 | biostudies-arrayexpress

Homeodomain proteins hierarchically specify neuronal diversity and synaptic connectivity

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

scRNA-seq of ferret cortical germinal zones from splenial gyrus and lateral sulcus (Borrell lab)

Project description:Diversity of cortical radial glia cells (RGCs) and their complex relationships to generate neurons in species with expanded germinal zones and a folded cortex, remains unclear. We used single-cell RNA sequencing (scRNA-seq) of microdissected cortical germinal layers (ventricular zone (VZ) and outer subventricular zone (OSVZ)), from two cortical regions (splenial gyrus (SG) and neighboring lateral sulcus (LS)) at two critical time points for ferret cortex development (embryonic day (E) 34 and postnatal day (P) 1) to distinguish the molecular diversity of progenitors and newborn neurons, and study their transcriptomic trajectories.

2024-03-27 | GSE219254 | GEO

Microarray analysis of perichondral and reserve growth plate zones

Project description:In the growth plate, the reserve and perichondral zones have been hypothesized to have similar functions, but their exact functions are poorly understood. Our hypothesis was that significant differential gene expression exists between perichondral and reserve chondrocytes that may differentiate the respective functions of these two zones. Normal Sprague-Dawley rat growth plate chondrocytes from the perichondral zone (PC), reserve zone (RZ), proliferative zone (PZ), and hypertrophic zone (HZ) were isolated by laser microdissection and then subjected to microarray analysis. In order to most comprehensively capture the unique features of the two zones, we analyzed both the most highly expressed genes and those that were most significantly different from the proliferative zone (PZ) as a single comparator. Keywords: cell specific expression profiles

2008-03-28 | GSE9537 | GEO

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