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Development (Cambridge, England) Jan 2011During nervous system development, axons generate branches to connect with multiple synaptic targets. As with axon growth and guidance, axon branching is tightly... (Review)
Review
During nervous system development, axons generate branches to connect with multiple synaptic targets. As with axon growth and guidance, axon branching is tightly controlled in order to establish functional neural circuits, yet the mechanisms that regulate this important process are less well understood. Here, we review recent advances in the study of several common branching processes in the vertebrate nervous system. By focusing on each step in these processes we illustrate how different types of branching are regulated by extracellular cues and neural activity, and highlight some common principles that underlie the establishment of complex neural circuits in vertebrate development.
Topics: Animals; Axons; Models, Neurological; Nervous System; Nervous System Physiological Phenomena; Neurogenesis; Neurons; Signal Transduction; Synapses; Vertebrates
PubMed: 21177340
DOI: 10.1242/dev.046441 -
Current Protocols in Neuroscience Sep 2019The axon initial segment (AIS) is the first 20- to 60-μm segment of the axon proximal to the soma of a neuron. This highly specialized subcellular domain is the...
The axon initial segment (AIS) is the first 20- to 60-μm segment of the axon proximal to the soma of a neuron. This highly specialized subcellular domain is the initiation site of the action potential and contains a high concentration of voltage-gated ion channels held in place by a complex nexus of scaffolding and regulatory proteins that ensure proper electrical activity of the neuron. Studies have shown that dysfunction of many AIS channels and scaffolding proteins occurs in a variety of neuropsychiatric and neurodegenerative diseases, raising the need to develop accurate methods for visualization and quantification of the AIS and its protein content in models of normal and disease conditions. In this article, we describe methods for immunolabeling AIS proteins in cultured neurons and brain slices as well as methods for quantifying protein expression and pattern distribution using fluorescent labeling of these proteins. © 2019 by John Wiley & Sons, Inc.
Topics: Action Potentials; Animals; Axon Initial Segment; Axons; Brain; Cells, Cultured; Neuroimaging; Neurons
PubMed: 31532918
DOI: 10.1002/cpns.78 -
Neuroscience Bulletin Aug 2014A typical neuron is comprised of an information input compartment, or the dendrites, and an output compartment, known as the axon. These two compartments are the... (Review)
Review
A typical neuron is comprised of an information input compartment, or the dendrites, and an output compartment, known as the axon. These two compartments are the structural basis for functional neural circuits. However, little is known about how dendritic and axonal growth are differentially regulated. Recent studies have uncovered two distinct types of regulatory mechanisms that differentiate dendritic and axonal growth: dedicated mechanisms and bimodal mechanisms. Dedicated mechanisms regulate either dendritespecific or axon-specific growth; in contrast, bimodal mechanisms direct dendritic and axonal development in opposite manners. Here, we review the dedicated and bimodal regulators identified by recent Drosophila and mammalian studies. The knowledge of these underlying molecular mechanisms not only expands our understanding about how neural circuits are wired, but also provides insights that will aid in the rational design of therapies for neurological diseases.
Topics: Animals; Axons; Dendrites; Drosophila; Drosophila Proteins; Humans; Intercellular Signaling Peptides and Proteins; Transcription Factors
PubMed: 25001617
DOI: 10.1007/s12264-014-1447-3 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... May 2020The intrinsic regrowth ability of injured neurons is essential for axon regeneration and functional recovery. Recently, numerous intrinsic pathways that regulate axon... (Review)
Review
The intrinsic regrowth ability of injured neurons is essential for axon regeneration and functional recovery. Recently, numerous intrinsic pathways that regulate axon regeneration have been discovered, among which the mitogen-activated protein kinase (MAPK) pathway and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway are arguably the best characterized examples. MAPK signaling pathway is involved in multiple processes including sensing injury signals, initiating and promoting axonal regrowth through regulating cytoskeleton dynamics and protein synthesis. The PI3K/Akt signaling pathway regulates axon regeneration mainly through gene transcription and translation. Combinatory manipulation of multiple regeneration-promoting signals can further improve the extend of axonal regrowth. This paper summarizes current progresses on axon regeneration studies in various organisms and discuss their potentials in promoting functional recovery .
Topics: Axons; Nerve Regeneration; Neurons; Phosphatidylinositol 3-Kinases; Regeneration; Signal Transduction
PubMed: 32621408
DOI: 10.3785/j.issn.1008-9292.2020.02.08 -
Experimental & Molecular Medicine Jan 2021Axon regeneration is orchestrated by many genes that are differentially expressed in response to injury. Through a comparative analysis of gene expression profiling,... (Review)
Review
Axon regeneration is orchestrated by many genes that are differentially expressed in response to injury. Through a comparative analysis of gene expression profiling, injury-responsive genes that are potential targets for understanding the mechanisms underlying regeneration have been revealed. As the efficiency of axon regeneration in both the peripheral and central nervous systems can be manipulated, we suggest that identifying regeneration-associated genes is a promising approach for developing therapeutic applications in vivo. Here, we review the possible roles of stem cell marker- or stemness-related genes in axon regeneration to gain a better understanding of the regeneration mechanism and to identify targets that can enhance regenerative capacity.
Topics: Animals; Axons; Humans; Nerve Regeneration; Nerve Tissue Proteins; Neural Stem Cells
PubMed: 33446881
DOI: 10.1038/s12276-020-00553-z -
Scientific Reports Nov 2022Light and optical techniques are widely used for the diagnosis and treatment of neurological diseases as advanced methods. Understanding the optical properties of...
Light and optical techniques are widely used for the diagnosis and treatment of neurological diseases as advanced methods. Understanding the optical properties of nervous tissue and nerve cells is vital. Using light sources in these methods raises significant challenges, such as finding the place of light transmission in nerve fibers that could be an appropriate substrate for neural signaling. The myelinated axons are a promising candidate for transmitting neural signals and light due to their waveguide structures. On the other hand, with the emergence of diseases such as multiple sclerosis and disorders within the production and transmission of nerve signals, because of the demyelination, understanding the properties of the myelinated axon as a waveguide is obtaining additional necessity. The present study aims to show that the myelinated axon's refractive index (RI) profile plays an essential role in transmitting the beams in it. According to the nerve fiber, RI profile and its similarity to depressed core fiber with lower RI of the core compared to the cladding, the behaviors of the nerve fiber based on anti-resonant reflecting optical waveguide structure are investigated by taking into account the realistic optical imperfections. Light launching to the myelin sheath and axon is shown by introducing the axon and myelin sheath as a waveguide in the presence of both axon and myelin with bends, myelin sheath variation, and node of Ranvier.
Topics: Nerve Fibers, Myelinated; Myelin Sheath; Axons
PubMed: 36369256
DOI: 10.1038/s41598-022-23580-4 -
The Journal of Biological Chemistry Mar 2022The dual leucine zipper kinase (DLK) is a key regulator of axon regeneration and degeneration in response to neuronal injury; however, regulatory mechanisms of the DLK...
The dual leucine zipper kinase (DLK) is a key regulator of axon regeneration and degeneration in response to neuronal injury; however, regulatory mechanisms of the DLK function via its interacting proteins are largely unknown. To better understand the molecular mechanism of DLK function, we performed yeast two-hybrid screening analysis and identified FK506-binding protein-like (FKBPL, also known as WAF-1/CIP1 stabilizing protein 39) as a DLK-binding protein. FKBPL binds to the kinase domain of DLK and inhibits its kinase activity. In addition, FKBPL induces DLK protein degradation through ubiquitin-dependent pathways. We further assessed other members in the FKBP protein family and found that FK506-binding protein 8 (FKBP8) also induced DLK degradation. We identified the lysine 271 residue in the kinase domain as a major site of DLK ubiquitination and SUMO3 conjugation and was thus responsible for regulating FKBP8-mediated proteasomal degradation that was inhibited by the substitution of the lysine 271 to arginine. FKBP8-mediated degradation of DLK is mediated by autophagy pathway because knockdown of Atg5 inhibited DLK destabilization. We show that in vivo overexpression of FKBP8 delayed the progression of axon degeneration and suppressed neuronal death after axotomy in sciatic and optic nerves. Taken together, this study identified FKBPL and FKBP8 as novel DLK-interacting proteins that regulate DLK stability via the ubiquitin-proteasome and lysosomal protein degradation pathways.
Topics: Axons; Leucine Zippers; Lysine; MAP Kinase Kinase Kinases; Nerve Degeneration; Nerve Regeneration; Tacrolimus Binding Proteins; Ubiquitin
PubMed: 35101451
DOI: 10.1016/j.jbc.2022.101647 -
Journal of Biomechanics Dec 2016In the first phase of axon growth, axons sprout from neuron bodies and are extended by the pull of the migrating growth cones towards their targets. Thereafter, once the...
In the first phase of axon growth, axons sprout from neuron bodies and are extended by the pull of the migrating growth cones towards their targets. Thereafter, once the target is reached, a lesser known second phase of axon growth ensues as the mechanical forces from the growth of the animal induce extension of the integrated axons in the process of forming tracts and nerves. Although there are several microscopic physics based models of the first phase of axon growth, to date, there are no models of the very different second phase. Here we propose a mathematical model for stretch growth of axon tracts in which the rate of production of proteins required for growth is dependent on the membrane tension. We assume that growth occurs all along the axon, and are able to predict the increase in axon cross-sectional area after they are rapidly stretched and held at a constant length for several hours. We show that there is a length dependent maximum stretching rate that an axon can sustain without disconnection in steady state when the axon length is primarily increased near the cell body. Our results could inform better design of stretch growth protocols to create transplantable axon tracts to repair the nervous system.
Topics: Algorithms; Animals; Axons; Cell Enlargement; Cells, Cultured; Growth Cones; Humans; Models, Biological; Neurons
PubMed: 27890538
DOI: 10.1016/j.jbiomech.2016.11.045 -
Current Opinion in Neurobiology Feb 2004Axons from the retina traverse different molecular territories as they navigate to the tectum. A single territory might span only a few cell diameters and harbour... (Review)
Review
Axons from the retina traverse different molecular territories as they navigate to the tectum. A single territory might span only a few cell diameters and harbour multiple guidance cues, many of which are beginning to be characterized. Also present in the pathway are 'modulators' that influence a growth cone's response to a coincident signal but do not guide growth directly. An emerging principle is that the growth cone, itself, changes molecularly as it journeys through the visual pathway. Growing retinal axons contain mRNAs, ubiquitinating and apoptotic enzymes, translation and degradation machinery. Guidance cues can trigger rapid and local synthesis, degradation and endocytosis of proteins, providing a fast and flexible way for growth cones to respond to cues in their microenvironment and to alter their responsiveness. The data raise the idea that the localized synthesis and downregulation of proteins might help to steer retinal axon growth and, further, might contribute to the changing character of a growth cone as it ages.
Topics: Animals; Axons; Endocytosis; Growth Cones; Humans; Retina; Visual Pathways
PubMed: 15018939
DOI: 10.1016/j.conb.2004.01.002 -
Journal of Neuroscience Methods Aug 2021Neurons broadcast electrical signals to distal brain regions through extensive axonal arbors. Genetically encoded calcium sensors permit the direct observation of action... (Review)
Review
Neurons broadcast electrical signals to distal brain regions through extensive axonal arbors. Genetically encoded calcium sensors permit the direct observation of action potential activity at axonal terminals, providing unique insights on the organization and function of neural projections. Here, we consider what information can be gleaned from axonal recordings made at scales ranging from the summed activity extracted from multi-cell axon projections to single boutons. In particular, we discuss the application of different recently developed multi photon and fiber photometry methods for recording neural activity in axons of rodents. We define experimental difficulties associated with imaging approaches in the axonal compartment and highlight the latest methodological advances for addressing these issues. Finally, we reflect on ways in which new technologies can be used in conjunction with axon calcium imaging to address current questions in neurobiology.
Topics: Action Potentials; Axons; Calcium; Humans; Neurons; Presynaptic Terminals
PubMed: 34119572
DOI: 10.1016/j.jneumeth.2021.109251