scholarly journals Trans-synaptic Fish-lips Signaling Prevents Misconnections between Non-synaptic Partner Olfactory Neurons

2019 ◽  
Author(s):  
Qijing Xie ◽  
Bing Wu ◽  
Jiefu Li ◽  
Hongjie Li ◽  
David J Luginbuhl ◽  
...  
Keyword(s):  
Olfactory Receptor ◽  
Neural Circuit ◽  
Transmembrane Protein ◽  
Fruit Fly ◽  
Projection Neuron ◽  
Olfactory Receptor Neuron ◽  
Projection Neurons ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
Circuit Assembly

AbstractOur understanding of the mechanisms of neural circuit assembly is far from complete. Identification of new wiring molecules with novel mechanisms of action will provide new insights into how complex and heterogeneous neural circuits assemble during development. Here, we performed an RNAi screen for cell-surface molecules and identified the leucine-rich-repeat containing transmembrane protein, Fish-lips (Fili), as a novel wiring molecule in the assembly of the Drosophila olfactory circuit. Fili contributes to the precise targeting of both olfactory receptor neuron (ORN) axons as well as projection neuron (PN) dendrites. Cell-type-specific expression and genetic analyses suggest that Fili sends a trans-synaptic repulsive signal to neurites of non-partner classes that prevent their targeting to inappropriate glomeruli in the antennal lobe.Significance StatementIn the fruit fly olfactory system, 50 classes of olfactory receptor neurons (ORNs) make precise synaptic connections with 50 classes of corresponding projection neurons (PNs). Identification of wiring molecules in this circuit can provide insight into understanding neural circuit assembly. This paper reports the role of a transmembrane protein, Fish-lips (Fili), in forming specific connections in this circuit. We found that some ORN axons are repelled by Fili, which is present on dendrites of non-matching PN class, preventing them from targeting inappropriate glomeruli. Similarly, some PN dendrites are repelled by Fili expressed by non-matching ORN class for their correct targeting. Together, these results suggest that Fili mediates repulsion between axons and dendrites of non-synaptic partners to ensure precise wiring patterns.

scholarly journals Transsynaptic Fish-lips signaling prevents misconnections between nonsynaptic partner olfactory neurons

2019 ◽  
Vol 116 (32) ◽  
pp. 16068-16073 ◽  
Author(s):  
Qijing Xie ◽  
Bing Wu ◽  
Jiefu Li ◽  
Chuanyun Xu ◽  
Hongjie Li ◽  
...  
Keyword(s):  
Neural Circuit ◽  
Transmembrane Protein ◽  
Small Subset ◽  
Projection Neurons ◽  
Specific Expression ◽  
Olfactory Neurons ◽  
Surface Molecules ◽  
Cell Type Specific Expression ◽  
Cell Type Specific ◽  
Receptor Neurons

Our understanding of the mechanisms of neural circuit assembly is far from complete. Identification of wiring molecules with novel mechanisms of action will provide insights into how complex and heterogeneous neural circuits assemble during development. In the Drosophila olfactory system, 50 classes of olfactory receptor neurons (ORNs) make precise synaptic connections with 50 classes of partner projection neurons (PNs). Here, we performed an RNA interference screen for cell surface molecules and identified the leucine-rich repeat–containing transmembrane protein known as Fish-lips (Fili) as a novel wiring molecule in the assembly of the Drosophila olfactory circuit. Fili contributes to the precise axon and dendrite targeting of a small subset of ORN and PN classes, respectively. Cell-type–specific expression and genetic analyses suggest that Fili sends a transsynaptic repulsive signal to neurites of nonpartner classes that prevents their targeting to inappropriate glomeruli in the antennal lobe.

scholarly journals Classifying Drosophila Olfactory Projection Neuron Subtypes by Single-cell RNA Sequencing

2017 ◽  
Author(s):  
Hongjie Li ◽  
Felix Horns ◽  
Bing Wu ◽  
Qijing Xie ◽  
Jiefu Li ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Neuronal Cell ◽  
Projection Neuron ◽  
Projection Neurons ◽  
Open Questions ◽  
Olfactory Glomeruli ◽  
Single Cell Rna Sequencing ◽  
Genes Encoding ◽  
Circuit Assembly

AbstractHow a neuronal cell type is defined and how this relates to its transcriptome are still open questions. The Drosophila olfactory projection neurons (PNs) are among the best-characterized neuronal types: Different PN classes target dendrites to distinct olfactory glomeruli and PNs of the same class exhibit indistinguishable anatomical and physiological properties. Using single-cell RNA-sequencing, we comprehensively characterized the transcriptomes of 40 PN classes and unequivocally identified transcriptomes for 6 classes. We found a new lineage-specific transcription factor that instructs PN dendrite targeting. Transcriptomes of closely-related PN classes exhibit the largest difference during circuit assembly, but become indistinguishable in adults, suggesting that neuronal subtype diversity peaks during development. Genes encoding transcription factors and cell-surface molecules are the most differentially expressed, indicating their central roles in specifying neuronal identity. Finally, we show that PNs use highly redundant combinatorial molecular codes to distinguish subtypes, enabling robust specification of cell identity and circuit assembly.

scholarly journals Early warning signals regarding environmental suitability in the Drosophila antenna

2017 ◽  
Author(s):  
Haoyang Rong ◽  
Prithwiraj Das ◽  
Adalee Lube ◽  
David Yang ◽  
Debajit Saha ◽  
...  
Keyword(s):  
Linear Combination ◽  
High Intensity ◽  
Olfactory Receptor ◽  
Fruit Fly ◽  
Olfactory Receptor Neuron ◽  
Protective Mechanism ◽  
List Type ◽  
Neural Excitability ◽  
Environmental Threats ◽  
Olfactory Stimuli

HighlightsA novel geotaxis assay showed high intensity odorant exposures are harmful to fliesRepulsion at high odor intensities can be a protective mechanismOlfactory receptor neuron (ORN) excitability abruptly changes with odor intensityA linear combination of ORN activities can robustly predict intensity-dependent behavioral repulsionSummaryThe olfactory system is uniquely positioned to warn an organism of environmental threats. Whether and how it encodes such information is not understood. Here, we examined this issue in the fruit fly Drosophila melanogaster. We found that intensity-dependent repulsion to chemicals safeguarded flies from harmful, high-intensity vapor exposures. To understand how sensory input changed as the odor valence switched from innocuous to threatening, we recorded from olfactory receptor neurons (ORNs) in the fly antenna. Primarily, we observed two response non-linearities: recruitment of non-active ORNs at higher intensities, and abrupt transitions in neural excitability from regular spiking to high-firing oscillatory regime. Although non-linearities observed in any single ORN was not a good indicator, a simple linear combination of firing events from multiple neurons provided robust recognition of threating/repulsive olfactory stimuli. In sum, our results reveal how information necessary to avoid environmental threats may also be encoded in the insect antenna.

scholarly journals Multi-glomerular projection of single olfactory receptor neurons is conserved among amphibians

2019 ◽  
Author(s):  
Lukas Weiss ◽  
Lucas D. Jungblut ◽  
Andrea G. Pozzi ◽  
Barbara S. Zielinski ◽  
Lauren A. O’Connell ◽  
...  
Keyword(s):  
Olfactory Receptor ◽  
Olfactory Receptor Neuron ◽  
Receptor Neuron ◽  
Projection Neurons ◽  
Amphibian Species ◽  
Odor Processing ◽  
Axonal Projections ◽  
Frog Species ◽  
Receptor Neurons ◽  
Jawless Fish

Individual receptor neurons in the peripheral olfactory organ extend long axons into the olfactory bulb forming synapses with projection neurons in spherical neuropil regions, called glomeruli. Generally, odor map formation and odor processing in all vertebrates is based on the assumption that receptor neuron axons exclusively connect to a single glomerulus without any axonal branching. We comparatively tested this hypothesis in multiple fish and amphibian species by applying sparse cell electroporation to trace single olfactory receptor neuron axons. Sea lamprey (jawless fish) and zebrafish (bony fish) support the unbranched axon concept, with 94% of axons terminating in single glomeruli. Contrastingly, axonal projections of the axolotl (salamander) branch extensively before entering up to six distinct glomeruli. Receptor neuron axons labeled in frog species (Pipidae, Bufonidae, Hylidae and Dendrobatidae) predominantly bifurcate before entering a glomerulus and 59% and 50% connect to multiple glomeruli in larval and post-metamorphotic animals, respectively. Independent of developmental stage, lifestyle and adaptations to specific habitats, it seems to be a common feature of amphibian olfactory receptor neuron axons to frequently bifurcate and connect to multiple glomeruli. Our study challenges the unbranched axon concept as a universal vertebrate feature and it is conceivable that also later diverging vertebrates deviate from it. We propose that this unusual wiring logic evolved around the divergence of the terrestrial tetrapod lineage from its aquatic ancestors and could be the basis of an alternative way of odor processing.Abstract Figure

scholarly journals Single-cell RNAseq reveals cell adhesion molecule profiles in electrophysiologically defined neurons

2016 ◽  
Vol 113 (35) ◽  
pp. E5222-E5231 ◽  
Author(s):  
Csaba Földy ◽  
Spyros Darmanis ◽  
Jason Aoto ◽  
Robert C. Malenka ◽  
Stephen R. Quake ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Single Cell ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Expression Profiles ◽  
Projection Neurons ◽  
Specific Expression ◽  
Synaptic Specificity ◽  
Genes Encoding ◽  
Cell Type Specific Expression

In brain, signaling mediated by cell adhesion molecules defines the identity and functional properties of synapses. The specificity of presynaptic and postsynaptic interactions that is presumably mediated by cell adhesion molecules suggests that there exists a logic that could explain neuronal connectivity at the molecular level. Despite its importance, however, the nature of such logic is poorly understood, and even basic parameters, such as the number, identity, and single-cell expression profiles of candidate synaptic cell adhesion molecules, are not known. Here, we devised a comprehensive list of genes involved in cell adhesion, and used single-cell RNA sequencing (RNAseq) to analyze their expression in electrophysiologically defined interneurons and projection neurons. We compared the cell type-specific expression of these genes with that of genes involved in transmembrane ion conductances (i.e., channels), exocytosis, and rho/rac signaling, which regulates the actin cytoskeleton. Using these data, we identified two independent, developmentally regulated networks of interacting genes encoding molecules involved in cell adhesion, exocytosis, and signal transduction. Our approach provides a framework for a presumed cell adhesion and signaling code in neurons, enables correlating electrophysiological with molecular properties of neurons, and suggests avenues toward understanding synaptic specificity.

scholarly journals A cell type‐specific expression map of NCoR1 and SMRT transcriptional co‐repressors in the mouse brain

2020 ◽  
Vol 528 (13) ◽  
pp. 2218-2238 ◽  
Author(s):  
Attilio Iemolo ◽  
Patricia Montilla‐Perez ◽  
I‐Chi Lai ◽  
Yinuo Meng ◽  
Syreeta Nolan ◽  
...  
Keyword(s):  
Mouse Brain ◽  
Cell Type ◽  
Specific Expression ◽  
Cell Type Specific Expression ◽  
A Cell ◽  
Cell Type Specific

scholarly journals Murine Esophagus Expresses Glial-Derived Central Nervous System Antigens

2021 ◽  
Vol 22 (6) ◽  
pp. 3233
Author(s):  
Christopher Kapitza ◽  
Rittika Chunder ◽  
Anja Scheller ◽  
Katherine S. Given ◽  
Wendy B. Macklin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Schwann Cells ◽  
Glial Cells ◽  
Proteolipid Protein ◽  
Pcr Analysis ◽  
Specific Expression ◽  
Enteric Glial Cells ◽  
Cell Type Specific Expression ◽  
Long Time

Multiple sclerosis (MS) has been considered to specifically affect the central nervous system (CNS) for a long time. As autonomic dysfunction including dysphagia can occur as accompanying phenomena in patients, the enteric nervous system has been attracting increasing attention over the past years. The aim of this study was to identify glial and myelin markers as potential target structures for autoimmune processes in the esophagus. RT-PCR analysis revealed glial fibrillary acidic protein (GFAP), proteolipid protein (PLP), and myelin basic protein (MBP) expression, but an absence of myelin oligodendrocyte glycoprotein (MOG) in the murine esophagus. Selected immunohistochemistry for GFAP, PLP, and MBP including transgenic mice with cell-type specific expression of PLP and GFAP supported these results by detection of (1) GFAP, PLP, and MBP in Schwann cells in skeletal muscle and esophagus; (2) GFAP, PLP, but no MBP in perisynaptic Schwann cells of skeletal and esophageal motor endplates; (3) GFAP and PLP, but no MBP in glial cells surrounding esophageal myenteric neurons; and (4) PLP, but no GFAP and MBP in enteric glial cells forming a network in the esophagus. Our results pave the way for further investigations regarding the involvement of esophageal glial cells in the pathogenesis of dysphagia in MS.

scholarly journals Olfactory expression of trace amine-associated receptors requires cooperative cis-acting enhancers

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ami Shah ◽  
Madison Ratkowski ◽  
Alessandro Rosa ◽  
Paul Feinstein ◽  
Thomas Bozza
Keyword(s):  
Gene Expression ◽  
Large Family ◽  
Sequence Motifs ◽  
Specific Expression ◽  
Cis Acting ◽  
Conserved Sequence ◽  
Trace Amine ◽  
Sequence Elements ◽  
Cell Type Specific Expression ◽  
Cell Type Specific

AbstractOlfactory sensory neurons express a large family of odorant receptors (ORs) and a small family of trace amine-associated receptors (TAARs). While both families are subject to so-called singular expression (expression of one allele of one gene), the mechanisms underlying TAAR gene choice remain obscure. Here, we report the identification of two conserved sequence elements in the mouse TAAR cluster (T-elements) that are required for TAAR gene expression. We observed that cell-type-specific expression of a TAAR-derived transgene required either T-element. Moreover, deleting either element reduced or abolished expression of a subset of TAAR genes, while deleting both elements abolished olfactory expression of all TAARs in cis with the mutation. The T-elements exhibit several features of known OR enhancers but also contain highly conserved, unique sequence motifs. Our data demonstrate that TAAR gene expression requires two cooperative cis-acting enhancers and suggest that ORs and TAARs share similar mechanisms of singular expression.

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