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The Journal of Experimental Biology Feb 2015Polarized distribution of signaling molecules to axons and dendrites facilitates directional information flow in complex vertebrate nervous systems. The topic we address... (Review)
Review
Polarized distribution of signaling molecules to axons and dendrites facilitates directional information flow in complex vertebrate nervous systems. The topic we address here is when the key aspects of neuronal polarity evolved. All neurons have a central cell body with thin processes that extend from it to cover long distances, and they also all rely on voltage-gated ion channels to propagate signals along their length. The most familiar neurons, those in vertebrates, have additional cellular features that allow them to send directional signals efficiently. In these neurons, dendrites typically receive signals and axons send signals. It has been suggested that many of the distinct features of axons and dendrites, including the axon initial segment, are found only in vertebrates. However, it is now becoming clear that two key cytoskeletal features that underlie polarized sorting, a specialized region at the base of the axon and polarized microtubules, are found in invertebrate neurons as well. It thus seems likely that all bilaterians generate axons and dendrites in the same way. As a next step, it will be extremely interesting to determine whether the nerve nets of cnidarians and ctenophores also contain polarized neurons with true axons and dendrites, or whether polarity evolved in concert with the more centralized nervous systems found in bilaterians.
Topics: Animals; Axons; Biological Evolution; Cytoskeleton; Dendrites; Invertebrates; Microtubules; Neurons
PubMed: 25696820
DOI: 10.1242/jeb.112359 -
Cell Reports Feb 2024Inflammation is closely associated with many neurodegenerative disorders. Yet, whether inflammation causes, exacerbates, or responds to neurodegeneration has been...
Inflammation is closely associated with many neurodegenerative disorders. Yet, whether inflammation causes, exacerbates, or responds to neurodegeneration has been challenging to define because the two processes are so closely linked. Here, we disentangle inflammation from the axon damage it causes by individually blocking cytotoxic T cell function and axon degeneration. We model inflammatory damage in mouse skin, a barrier tissue that, despite frequent inflammation, must maintain proper functioning of a dense array of axon terminals. We show that sympathetic axons modulate skin inflammation through release of norepinephrine, which suppresses activation of γδ T cells via the β2 adrenergic receptor. Strong inflammatory stimulation-modeled by application of the Toll-like receptor 7 agonist imiquimod-causes progressive γδ T cell-mediated, Sarm1-dependent loss of these immunosuppressive sympathetic axons. This removes a physiological brake on T cells, initiating a positive feedback loop of enhanced inflammation and further axon damage.
Topics: Animals; Mice; Feedback; Inflammation; Axons; Dermatitis; Presynaptic Terminals
PubMed: 38310514
DOI: 10.1016/j.celrep.2024.113721 -
International Journal of Molecular... Aug 2021During neuronal development and regeneration axons extend a cytoskeletal-rich structure known as the growth cone, which detects and integrates signals to reach its final... (Review)
Review
During neuronal development and regeneration axons extend a cytoskeletal-rich structure known as the growth cone, which detects and integrates signals to reach its final destination. The guidance cues "signals" bind their receptors, activating signaling cascades that result in the regulation of the growth cone cytoskeleton, defining growth cone advance, pausing, turning, or collapse. Even though much is known about guidance cues and their isolated mechanisms during nervous system development, there is still a gap in the understanding of the crosstalk between them, and about what happens after nervous system injuries. After neuronal injuries in mammals, only axons in the peripheral nervous system are able to regenerate, while the ones from the central nervous system fail to do so. Therefore, untangling the guidance cues mechanisms, as well as their behavior and characterization after axotomy and regeneration, are of special interest for understanding and treating neuronal injuries. In this review, we present findings on growth cone guidance and canonical guidance cues mechanisms, followed by a description and comparison of growth cone pathfinding mechanisms after axotomy, in regenerative and non-regenerative animal models.
Topics: Animals; Axon Guidance; Axons; Axotomy; Growth Cones; Humans; Nerve Regeneration; Signal Transduction
PubMed: 34361110
DOI: 10.3390/ijms22158344 -
Current Opinion in Neurobiology Feb 2011Axon regeneration has long been studied in vertebrate model organisms and neuronal cultures. Recent development of axon regeneration paradigms in genetic model... (Review)
Review
Axon regeneration has long been studied in vertebrate model organisms and neuronal cultures. Recent development of axon regeneration paradigms in genetic model organisms, such as Caenorhabditis elegans, Drosophila and zebrafish, has opened an exciting field for in vivo functional dissection of regeneration pathways. Studies in these organisms have discovered essential genes and pathways for axon regrowth. The conservation of these genes crossing animal phyla suggests mechanistic relevance to higher organisms. The power of genetic approaches in these organisms makes large-scale genetic and pharmacological screens feasible and can greatly accelerate the mechanistic understanding of axon regeneration.
Topics: Animals; Axons; Humans; Nerve Regeneration
PubMed: 20832288
DOI: 10.1016/j.conb.2010.08.010 -
Current Opinion in Neurobiology Dec 2013A remarkable feature of nervous system development is the ability of axons emerging from newly formed neurons to traverse, by cellular scale, colossal distances to... (Review)
Review
A remarkable feature of nervous system development is the ability of axons emerging from newly formed neurons to traverse, by cellular scale, colossal distances to appropriate targets. The earliest axons achieve this in an essentially axon-free environment, but the vast majority of axons eventually grow along a scaffold of nerve tracts created by earlier extending axons. Signal exchange between sequentially or simultaneously extending axons may well represent the predominant mode of axonal navigation, but proportionally few efforts have so far been directed at deciphering the underlying mechanisms. This review intends to provide a conceptual update on the cellular and molecular principles driving axon-axon interactions, with emphasis on those contributing to the fidelity of axonal navigation, sorting and connectivity during nerve and circuit assembly.
Topics: Animals; Axons; Cell Communication; Humans; Neurogenesis; Signal Transduction
PubMed: 23973157
DOI: 10.1016/j.conb.2013.08.004 -
Current Opinion in Neurobiology Dec 2018Understanding how neurons form, extend, and navigate their finger-like axonal and dendritic processes is crucial for developing therapeutics for the diseased and damaged... (Review)
Review
Understanding how neurons form, extend, and navigate their finger-like axonal and dendritic processes is crucial for developing therapeutics for the diseased and damaged brain. Although less well appreciated, many other types of cells also send out similar finger-like projections. Indeed, unlike neuronal specific phenomena such as synapse formation or synaptic transmission, an important issue for thought is that this critical long-standing question of how a cellular process like an axon or dendrite forms and extends is not primarily a neuroscience problem but a cell biological problem. In that case, the use of simple cellular processes - such as the bristle cell process of Drosophila - can aid in the fight to answer these critical questions. Specifically, determining how a model cellular process is generated can provide a framework for manipulations of all types of membranous process-containing cells, including different types of neurons.
Topics: Animals; Axons; Cell Biology; Models, Biological; Neurosciences
PubMed: 30248549
DOI: 10.1016/j.conb.2018.08.004 -
Neuroscience Letters Apr 2019Neurons are long-lived and highly polarized cells that depend on autophagy to maintain cellular homeostasis. The robust, constitutive biogenesis of autophagosomes in the... (Review)
Review
Neurons are long-lived and highly polarized cells that depend on autophagy to maintain cellular homeostasis. The robust, constitutive biogenesis of autophagosomes in the distal axon occurs via a conserved pathway that is required to maintain functional synapses and prevent axon degeneration. Autophagosomes are formed de novo at the axon terminal in a stepwise assembly process, engulfing mitochondrial fragments, aggregated proteins, and bulk cytosol in what appears to be a nonselective uptake mechanism. Following formation, autophagosomes fuse with late endosomes/lysosomes and then are rapidly and efficiently transported along the axon toward the soma, driven by the microtubule motor cytoplasmic dynein. Motile autophagosomes mature to autolysosomes in transit by fusing with additional late endosomes/lysosomes, arriving at the soma as fully competent degradative organelles. Misregulation of neuronal autophagy leads to axonal degeneration and synaptic destabilization, and has been implicated in neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and ALS.
Topics: Animals; Autophagosomes; Autophagy; Axons; Central Nervous System; Endosomes; Homeostasis; Humans; Lysosomes; Neurodegenerative Diseases; Neurons; Protein Transport
PubMed: 29548988
DOI: 10.1016/j.neulet.2018.03.025 -
Neuroscience Bulletin Aug 2014Precise modulation of the cytoskeleton is involved in a variety of cellular processes including cell division, migration, polarity, and adhesion. In developing... (Review)
Review
Precise modulation of the cytoskeleton is involved in a variety of cellular processes including cell division, migration, polarity, and adhesion. In developing post-mitotic neurons, extracellular guidance cues not only trigger signaling cascades that act at a distance to indirectly regulate microtubule distribution, and assembly and disassembly in the growth cone, but also directly modulate microtubule stability and dynamics through coupling of guidance receptors with microtubules to control growth-cone turning. Microtubule-associated proteins including classical microtubule-associated proteins and microtubule plus-end tracking proteins are required for modulating microtubule dynamics to influence growth-cone steering. Multiple key signaling components, such as calcium, small GTPases, glycogen synthase kinase-3β, and c-Jun N-terminal kinase, link upstream signal cascades to microtubule stability and dynamics in the growth cone to control axon outgrowth and projection. Understanding the functions and regulation of microtubule dynamics in the growth cone provides new insights into the molecular mechanisms of axon guidance.
Topics: Animals; Axons; Growth Cones; Humans; Microtubule-Associated Proteins; Microtubules; Nerve Growth Factors; Signal Transduction; Tubulin
PubMed: 24968808
DOI: 10.1007/s12264-014-1444-6 -
Trends in Neurosciences Mar 2009Axon-guidance-pathway molecules are involved in connectivity and repair throughout life (beyond guiding brain wiring during fetal development). One study found that... (Review)
Review
Axon-guidance-pathway molecules are involved in connectivity and repair throughout life (beyond guiding brain wiring during fetal development). One study found that variations (single-nucleotide polymorphisms [SNPs]) in axon-guidance-pathway genes were predictive of three Parkinson's disease (PD) outcomes (susceptibility, survival free of PD and age at onset of PD) in genome-wide association (GWA) datasets. The axon-guidance-pathway genes DCC, EPHB1, NTNG1, SEMA5A and SLIT3 were represented by SNPs predicting PD outcomes. Beyond GWA analyses, we also present relevant neurobiological roles of these axon-guidance-pathway molecules and consider mechanisms by which abnormal axon-guidance-molecule signaling can cause loss of connectivity and, ultimately, PD. Novel drugs and treatments could emerge from this new understanding.
Topics: Animals; Axons; Humans; Neural Pathways; Neurodegenerative Diseases; Neurons; Synapses
PubMed: 19162339
DOI: 10.1016/j.tins.2008.11.006 -
Current Biology : CB Jul 2021Neuronal injury can cause mitochondrial damage, leading to reduced energy production, decreased Ca storage capacity, and increased reactive oxygen species. A new study...
Neuronal injury can cause mitochondrial damage, leading to reduced energy production, decreased Ca storage capacity, and increased reactive oxygen species. A new study reveals a mechanism to trigger the axonal transport of previously anchored mitochondria and promote neuroprotection and axon regeneration by replacing damaged with functional mitochondria.
Topics: Axonal Transport; Axons; Nerve Regeneration; Neurobiology; Neurons
PubMed: 34314722
DOI: 10.1016/j.cub.2021.06.014