Glia dictate pioneer axon trajectories in the Drosophila embryonic CNS

Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 393-402 ◽  
Author(s):  
A. Hidalgo ◽  
G.E. Booth
Keyword(s):  
Axon Guidance ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Cell Types ◽  
Growth Cones ◽  
Neuronal Cell Bodies ◽  
Direct Formation ◽  
Pioneer Neurons ◽  
Embryonic Cns ◽  
Made In

Whereas considerable progress has been made in understanding the molecular mechanisms of axon guidance across the midline, it is still unclear how the axonal trajectories of longitudinal pioneer neurons, which never cross the midline, are established. Here we show that longitudinal glia of the embryonic Drosophila CNS direct formation of pioneer axon pathways. By ablation and analysis of glial cells missing mutants, we demonstrate that glia are required for two kinds of processes. Firstly, glia are required for growth cone guidance, although this requirement is not absolute. We show that the route of extending growth cones is rich in neuronal cell bodies and glia, and also in long processes from both these cell types. Interactions between neurons, glia and their long processes orient extending growth cones. Secondly, glia direct the fasciculation and defasciculation of axons, which pattern the pioneer pathways. Together these events are essential for the selective fasciculation of follower axons along the longitudinal pathways.

scholarly journals Visualisation of ribosomes in Drosophila axons using Ribo-BiFC

2019 ◽  
Author(s):  
Anand K Singh ◽  
Akilu Abdullahi ◽  
Matthias Soller ◽  
Alexandre David ◽  
Saverio Brogna
Keyword(s):  
Ribosomal Proteins ◽  
Neuronal Cell ◽  
Growth Cones ◽  
Distal Portion ◽  
Bimolecular Fluorescence Complementation ◽  
Improved Method ◽  
80S Ribosome ◽  
Optic Stalk ◽  
Neuronal Cell Bodies ◽  
Drosophila Cells

AbstractRates of protein synthesis and the number of translating ribosomes vary greatly between different cells in various cell states. The distribution of assembled, and potentially translating, ribosomes within cells can be visualised in Drosophila by using Bimolecular Fluorescence Complementation (BiFC) to monitor the interaction between tagged pairs of 40S and 60S ribosomal proteins (RPs) that are close neighbours across inter-subunit junctions in the assembled 80S ribosome. Here we describe transgenes that express two novel RP pairs tagged with Venus-based BiFC fragments that considerably increase the sensitivity of this technique that we termed Ribo-BiFC. This improved method should provide a convenient way of monitoring the local distribution of ribosomes in most Drosophila cells and we suggest that could be implemented in other organisms. We visualized 80S ribosomes in larval photoreceptors and in other neurons. Assembled ribosomes are most abundant in the various neuronal cell bodies, but they are also present along the lengths of axons and are concentrated in growth cones of larval and pupal photoreceptors. Surprisingly, there is relatively less puromycin incorporation in the distal portion of axons in the optic stalk, suggesting that some of the ribosomes that have started translation may not be engaged in elongation in axons that are still growing.

Glia maintain follower neuron survival during Drosophila CNS development

Development ◽  
2000 ◽  
Vol 127 (2) ◽  
pp. 237-244 ◽  
Author(s):  
G.E. Booth ◽  
E.F. Kinrade ◽  
A. Hidalgo
Keyword(s):  
Axon Guidance ◽  
Neuronal Survival ◽  
Cell Number ◽  
Cns Development ◽  
Neuronal Fate ◽  
Missing Gene ◽  
Pioneer Neurons ◽  
Longitudinal Axon ◽  
Glial Function ◽  
Embryonic Cns

While survival of CNS neurons appears to depend on multiple neuronal and non-neuronal factors, it remains largely unknown how neuronal survival is controlled during development. Here we show that glia regulate neuronal survival during formation of the Drosophila embryonic CNS. When glial function is impaired either by mutation of the glial cells missing gene, which transforms glia toward a neuronal fate, or by targeted genetic glial ablation, neuronal death is induced non-autonomously. Pioneer neurons, which establish the first longitudinal axon fascicles, are insensitive to glial depletion whereas the later extending follower neurons die. This differential requirement of neurons for glia is instructive in patterning and links control of cell number with axon guidance during CNS development.

scholarly journals Phagocytic Activities of Reactive Microglia and Astrocytes Associated with Prion Diseases Are Dysregulated in Opposite Directions

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1728
Author(s):  
Anshuman Sinha ◽  
Rajesh Kushwaha ◽  
Kara Molesworth ◽  
Olga Mychko ◽  
Natallia Makarava ◽  
...  
Keyword(s):  
Prion Diseases ◽  
Neuronal Cell ◽  
Cell Types ◽  
Reactive Microglia ◽  
Neuronal Cell Bodies ◽  
Myelin Debris ◽  
Neurotoxic Effects ◽  
The One ◽  
The Brain ◽  
Phagocytic Uptake

Phagocytosis is one of the most important physiological functions of the glia directed at maintaining a healthy, homeostatic environment in the brain. Under a homeostatic environment, the phagocytic activities of astrocytes and microglia are tightly coordinated in time and space. In neurodegenerative diseases, both microglia and astrocytes contribute to neuroinflammation and disease pathogenesis, however, whether their phagocytic activities are up- or downregulated in reactive states is not known. To address this question, this current study isolated microglia and astrocytes from C57BL/6J mice infected with prions and tested their phagocytic activities in live-cell imaging assays that used synaptosomes and myelin debris as substrates. The phagocytic uptake by the reactive microglia was found to be significantly upregulated, whereas that of the reactive astrocytes was strongly downregulated. The up- and downregulation of phagocytosis by the two cell types were observed irrespective of whether disease-associated synaptosomes, normal synaptosomes, or myelin debris were used in the assays, indicating that dysregulations are dictated by cell reactive states, not substrates. Analysis of gene expression confirmed dysregulation of phagocytic functions in both cell types. Immunostaining of animal brains infected with prions revealed that at the terminal stage of disease, neuronal cell bodies were subject to engulfment by reactive microglia. This study suggests that imbalance in the phagocytic activities of the reactive microglia and astrocytes, which are dysregulated in opposite directions, is likely to lead to excessive microglia-mediated neuronal death on the one hand, and the inability of astrocytes to clear cell debris on the other hand, contributing to the neurotoxic effects of glia as a whole.

scholarly journals Alcohol causes lasting differential transcription in Drosophila mushroom body neurons

2019 ◽  
Author(s):  
Emily Petruccelli ◽  
Nicolas Ledru ◽  
Karla R. Kaun
Keyword(s):  
Mushroom Body ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Cell Types ◽  
Memory Encoding ◽  
Sensory Cues ◽  
New Methods ◽  
Specific Regulation ◽  
Context Specific ◽  
Differential Transcription

AbstractRepeated alcohol experiences can produce long-lasting memories for sensory cues associated with intoxication. These memories can ultimately trigger relapse in individuals recovering from alcohol use disorder (AUD). The molecular mechanisms by which alcohol changes memories to become long-lasting and inflexible remain unclear. New methods to analyze gene expression within precise neuronal cell-types can provide further insight towards AUD prevention and treatment. Here, we employed genetic tools in Drosophila melanogaster to investigate the lasting consequences of ethanol on transcription in memory-encoding neurons. Drosophila rely on mushroom body (MB) neurons to make associative memories, including memories of ethanol-associated sensory cues. Differential expression analyses found that distinct transcripts, but not genes, in the MB were associated with experiencing ethanol alone compared to forming a memory of an odor cue associated with ethanol. These findings reveal the dynamic and highly context-specific regulation of splicing associated with encoding behavioral experiences. Our data thus demonstrate that alcohol can have lasting effects on transcription and RNA processing during memory formation, and identify new transcript targets for future AUD and addiction investigation.

scholarly journals A multicellular rosette-mediated collective dendrite extension

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Li Fan ◽  
Ismar Kovacevic ◽  
Maxwell G Heiman ◽  
Zhirong Bao
Keyword(s):  
Adhesion Molecules ◽  
Molecular Mechanisms ◽  
Neural Circuits ◽  
Sensory Nerve ◽  
Neuronal Cell ◽  
Sensory Organ ◽  
Neurite Extension ◽  
C Elegans ◽  
Neuronal Cell Bodies

Coordination of neurite morphogenesis with surrounding tissues is crucial to the establishment of neural circuits, but the underlying cellular and molecular mechanisms remain poorly understood. We show that neurons in a C. elegans sensory organ, called the amphid, undergo a collective dendrite extension to form the sensory nerve. The amphid neurons first assemble into a multicellular rosette. The vertex of the rosette, which becomes the dendrite tips, is attached to the anteriorly migrating epidermis and carried to the sensory depression, extruding the dendrites away from the neuronal cell bodies. Multiple adhesion molecules including DYF-7, SAX-7, HMR-1 and DLG-1 function redundantly in rosette-to-epidermis attachment. PAR-6 is localized to the rosette vertex and dendrite tips, and promotes DYF-7 localization and dendrite extension. Our results suggest a collective mechanism of neurite extension that is distinct from the classical pioneer-follower model and highlight the role of mechanical cues from surrounding tissues in shaping neurites.

Development of a sensory afferent projection in the grasshopper embryo

Development ◽  
1981 ◽  
Vol 64 (1) ◽  
pp. 169-185
Author(s):  
Marty Shankland
Keyword(s):  
Sensory Neurons ◽  
Secondary Growth ◽  
Leading Edge ◽  
Growth Cones ◽  
Peripheral Neurons ◽  
Sensory Axons ◽  
Terminal Filament ◽  
Pioneer Neurons ◽  
Embryonic Cns ◽  
Prolonged Absence

The grasshopper's cereal nerve is established early in embryogenesis by an identified pair of peripheral neurons called the cereal pioneers. Like the peripheral pioneer neurons in other insect appendages, these two cells send their axons from the periphery to the rudimentary CNS and thus lay the foundation for a nerve that will later be followed by a large number of sensory axons. In this paper, cobalt fills of the primordial cereal nerve were used to characterize the disposition of these peripheral pioneer axons within the embryonic CNS. The pioneer axons stained by this technique terminate in ellipsoidal growth cones which have filopodia radiating from the leading edge and a single long terminal filament pointing along the path the axon is taking. The growing axons also bear filopodia along their sides, but these structures disappear as the cells mature. The pioneer axons of the cereal nerve make an abrupt turn where they first enter the ganglion rudiment and join the axons of the primary longitudinal tract. The pioneers then grow along this tract for several hundred microns without forming secondary growth cones or branches. This prolonged absence of central arborization distinguishes the peripheral pioneer axons from the axons of later-arising epidermal sensory neurons.

scholarly journals Cell migration and axon guidance at the border between central and peripheral nervous system

Science ◽  
2019 ◽  
Vol 365 (6456) ◽  
pp. eaaw8231 ◽  
Author(s):  
Tracey A. C. S. Suter ◽  
Alexander Jaworski
Keyword(s):  
Nervous System ◽  
Cell Migration ◽  
Embryonic Development ◽  
Axon Guidance ◽  
Peripheral Nervous System ◽  
Glial Cell ◽  
Molecular Mechanisms ◽  
Control Cell ◽  
Cell Types ◽  
Open Questions

The central and peripheral nervous system (CNS and PNS, respectively) are composed of distinct neuronal and glial cell types with specialized functional properties. However, a small number of select cells traverse the CNS-PNS boundary and connect these two major subdivisions of the nervous system. This pattern of segregation and selective connectivity is established during embryonic development, when neurons and glia migrate to their destinations and axons project to their targets. Here, we provide an overview of the cellular and molecular mechanisms that control cell migration and axon guidance at the vertebrate CNS-PNS border. We highlight recent advances on how cell bodies and axons are instructed to either cross or respect this boundary, and present open questions concerning the development and plasticity of the CNS-PNS interface.

scholarly journals Two adhesive systems cooperatively regulate axon ensheathment and myelin growth in the CNS

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Minou Djannatian ◽  
Sebastian Timmler ◽  
Martina Arends ◽  
Manja Luckner ◽  
Marie-Theres Weil ◽  
...  
Keyword(s):  
Processing Speed ◽  
Spatial Organization ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Leading Edge ◽  
Neural Processing ◽  
Adhesive Systems ◽  
Molecular Analyses ◽  
Neuronal Cell Bodies ◽  
Internodal Segment

Abstract Central nervous system myelin is a multilayered membrane produced by oligodendrocytes to increase neural processing speed and efficiency, but the molecular mechanisms underlying axonal selection and myelin wrapping are unknown. Here, using combined morphological and molecular analyses in mice and zebrafish, we show that adhesion molecules of the paranodal and the internodal segment work synergistically using overlapping functions to regulate axonal interaction and myelin wrapping. In the absence of these adhesive systems, axonal recognition by myelin is impaired with myelin growing on top of previously myelinated fibers, around neuronal cell bodies and above nodes of Ranvier. In addition, myelin wrapping is disturbed with the leading edge moving away from the axon and in between previously formed layers. These data show how two adhesive systems function together to guide axonal ensheathment and myelin wrapping, and provide a mechanistic understanding of how the spatial organization of myelin is achieved.

scholarly journals The Aryl Hydrocarbon Receptor and the Nervous System

2018 ◽  
Vol 19 (9) ◽  
pp. 2504 ◽  
Author(s):  
Ludmila Juricek ◽  
Xavier Coumoul
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Molecular Mechanisms ◽  
Neuronal Cell ◽  
Cell Types ◽  
Dendritic Morphology ◽  
Metabolizing Enzymes ◽  
Common Features ◽  
Aryl Hydrocarbon ◽  
The Common ◽  
Neuronal Proliferation

The aryl hydrocarbon receptor (or AhR) is a cytoplasmic receptor of pollutants. It translocates into the nucleus upon binding to its ligands, and forms a heterodimer with ARNT (AhR nuclear translocator). The heterodimer is a transcription factor, which regulates the transcription of xenobiotic metabolizing enzymes. Expressed in many cells in vertebrates, it is mostly present in neuronal cell types in invertebrates, where it regulates dendritic morphology or feeding behavior. Surprisingly, few investigations have been conducted to unravel the function of the AhR in the central or peripheral nervous systems of vertebrates. In this review, we will present how the AhR regulates neural functions in both invertebrates and vertebrates as deduced mainly from the effects of xenobiotics. We will introduce some of the molecular mechanisms triggered by the well-known AhR ligand, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), which impact on neuronal proliferation, differentiation, and survival. Finally, we will point out the common features found in mice that are exposed to pollutants, and in AhR knockout mice.

scholarly journals A multicellular rosette-mediated collective dendrite extension

2018 ◽  
Author(s):  
Li Fan ◽  
Ismar Kovacevic ◽  
Maxwell Heiman ◽  
Zhirong Bao
Keyword(s):  
Adhesion Molecules ◽  
Molecular Mechanisms ◽  
Neural Circuits ◽  
Sensory Nerve ◽  
Neuronal Cell ◽  
Sensory Organ ◽  
Neurite Extension ◽  
C Elegans ◽  
Neuronal Cell Bodies

Coordination of neurite morphogenesis with surrounding tissues is crucial to the establishment of neural circuits, but the underlying cellular and molecular mechanisms remain poorly understood. We show that neurons in a C. elegans sensory organ, called the amphid, undergo a collective dendrite extension to initiate formation of the sensory nerve. The amphid neurons first assemble into a multicellular rosette. The vertex of the rosette, which becomes the dendrite tips, is attached to the anteriorly migrating epidermis and carried to the sensory depression, extruding the dendrites away from the neuronal cell bodies. Multiple adhesion molecules including DYF-7, SAX-7, HMR-1 and DLG-1 function redundantly in rosette-to-epidermis attachment. PAR-6 is localized to the rosette vertex and dendrite tips, and promotes DYF-7 localization and dendrite extension. Our results suggest a collective mechanism of neurite extension that is distinct from the classical pioneer-follower model and highlight the role of mechanical cues from surrounding tissues in shaping neurites.

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