Cell-type-specific genetic tools for the Drosophila central complex and their use to investigate neuropeptide expression and sleep regulation.
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE271123 | GEO | 2024/08/31
REPOSITORIES: GEO
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Project description:In both invertebrates such as Drosophila and vertebrates such as mouse or human, the brain contains the most diverse population of cell types of any tissue. It is generally accepted that transcriptional diversity is an early step in generating neuronal and glial diversity, followed by the establishment of a unique gene expression profile that determines morphology, connectivity, and function. In Drosophila, there are two types of neural stem cells, called Type 1 (T1) and Type 2 (T2) neuroblasts. In contrast to T1 neuroblasts, T2 neuroblasts generate intermediate neural progenitors (INPs) that expand the number and diversity of cell types. The diversity of T2-derived neurons contributes a large portion of the central complex (CX), a conserved brain region that plays a role in sensorimotor integration. Recent work has revealed much of the connectome of the CX, but how this connectome is assembled remains unclear. Mapping the transcriptional diversity of neurons derived from T2 neuroblasts is a necessary step in linking transcriptional profile to the assembly of the adult brain. Here we perform single nuclei RNA sequencing of T2 neuroblast-derived adult neurons and glia. We identify clusters containing all known classes of glia, clusters that are male/female enriched, and 161 neuron-specific clusters. We map neurotransmitter and neuropeptide expression and identify unique transcription factor combinatorial codes for each cluster (presumptive neuron subtype). This is a necessary step that directs functional studies to determine whether each transcription factor combinatorial code specifies a distinct neuron type within the CX. We map several columnar neuron subtypes to distinct clusters and identify two neuronal classes (NPF+ and AstA+) that both map to two closely related clusters. Our data support the hypothesis that each transcriptional cluster represents one or a few closely related neuron subtypes.
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Project description:Neural communication requires both fast-acting neurotransmitters and neuromodulators that function on slower timescales to communicate. Endogenous bioactive peptides, often called “neuropeptides,” comprise the largest and most diverse class of neuromodulators that mediate crosstalk between the brain and peripheral tissues to regulate physiology and behaviors conserved across the animal kingdom. Neuropeptide signaling can be terminated through receptor binding and internalization or degradation by extracellular enzymes called neuropeptidases. Inactivation by neuropeptidases can shape the dynamics of signaling in vivo by specifying both the duration of signaling and the anatomic path neuropeptides can travel before they are degraded. For most neuropeptides, the identity of the relevant inactivating peptidase(s) is unknown. Here, we established a screening platform in C. elegans utilizing mass spectrometry-based peptidomics to discover neuropeptidases and simultaneously profile the in vivo specificity of these enzymes against each of more than 250 endogenous peptides. We identified NEP-2, a worm ortholog of the mammalian peptidase neprilysin-2, and demonstrated that it regulates specific neuropeptides, including those in the egg-laying circuit. We found that NEP-2 is required in muscle cells to regulate signals from neurons to modulate both behavior and health in the reproductive system. Taken together, our results demonstrate that peptidases, which are an important node of regulation in neuropeptide signaling, affect the dynamics of signaling to impact behavior, physiology, and aging.
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2012-10-12 | E-GEOD-41510 | biostudies-arrayexpress
Project description:One of the key aspects of neuronal differentiation is the array of neurotransmitters and neurotransmitter receptors that each neuron possesses. One important goal of developmental neuroscience is to understand how these differentiated properties are established during development. In this paper, we use fluorescence activated cell sorting and RNA-seq to determine the transcriptome of the Drosophila CNS midline cells, which consist of a small number of well-characterized neurons and glia. These data revealed that midline cells express 9 neuropeptide precursor genes, 13 neuropeptide receptor genes, and 31 small-molecule neurotransmitter receptor genes. In situ hybridization and high-resolution confocal analyses were carried-out to determine the midline cell identity for these neuropeptides and the neuropeptide receptors. The results revealed a surprising level of diversity. Neuropeptide genes are expressed in a variety of midline cell types, including motoneurons, GABAergic interneurons, and midline glia. These data revealed previously unknown functional differences among the highly-related iVUM neurons. There also exist segmental differences in expression for the same neuronal sub-type. Similar experiments on midline-expressed neuropeptide receptor genes reveal considerable diversity in synaptic inputs. Multiple receptor types were expressed in midline interneurons and motoneurons, and, in one case, link feeding behavior to gut peristalsis and locomotion. There were also segmental differences, variations between the 3 iVUMs, and three hormone receptor genes were broadly expressed in most midline cells. The Drosophila Castor transcription factor is present at high levels in iVUM5, which is both GABAergic and expresses the short neuropeptide F precursor gene. Genetic and misexpression experiments indicated that castor specifically controls expression of the short neuropeptide F precursor gene, but does not affect iVUM cell fate or expression of Gad1. This indicates a novel function for castor in regulating neuropeptide gene expression.
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