Neurite

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A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because it can be difficult to tell axons from dendrites before differentiation is complete. [1]

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Neurite development

The development of a neurite (neuritogenesis) requires a complex interplay of both extracellular and intracellular signals. At every given point along a developing neurite, there are receptors detecting both positive and negative growth cues from every direction in the surrounding space. [2] The developing neurite sums together all of these growth signals in order to determine which direction the neurite will ultimately grow towards. [2] While not all of the growth signals are known, several have been identified and characterized. Among the known extracellular growth signals are netrin, a midline chemoattractant, and semaphorin, ephrin and collapsin, all inhibitors of neurite growth. [2] [3] [4]

Young neurites are often packed with microtubule bundles, the growth of which is stimulated by neurotrophic factors, such as nerve growth factor (NGF). [5] Tau proteins can aid in the stabilization of microtubules by binding to the microtubules, protecting them from microtubule severing proteins. [6] Even after the microtubules have stabilized, the cytoskeleton of the neuron remains dynamic. Actin filaments retain their dynamic properties in the neurite that will become the axon in order to push the microtubules bundles outward to extend the axon. [7] In all other neurites however, the actin filaments are stabilized by myosin. [8] This prevents the development of multiple axons.

The neural cell adhesion molecule N-CAM simultaneously combines with another N-CAM and a fibroblast growth factor receptor to stimulate the tyrosine kinase activity of that receptor to induce the growth of neurites. [9]

There are several software kits available to facilitate neurite tracing in images such as NeuronJ (an ImageJ plugin), [10] Neuromantic, [11] and the Neurolucida system. [12]

Weak endogenous electric fields may be used to both facilitate and direct the growth of projections from cell soma neurites, EFs of moderate strength have been used to direct and enhance neurite outgrowth in both murine, or mouse, and xenopus models. Co-culture of neurons with electrically aligned glial tissue also directs neurite outgrowth, as it is rich in neurotrophins that promote nerve growth [ citation needed ].

Establishing polarity

In vitro

Dorsal root ganglion neurons (left) extend neurites in a microfluidic device (time lapse over 48 hours). [13]

An undifferentiated mammalian neuron placed in culture will retract any neurites that it has already grown. [14] 0.5 to 1.5 days after being plated in culture, several minor neurites will begin to protrude out from the cell body. [14] Sometime between day 1.5 and day 3, one of the minor neurites begins to outgrow the other neurites significantly. This neurite will eventually become the axon. On days 4 to 7, the remaining minor neurites will begin differentiating into dendrites. [14] By day 7, the neuron should be completely polarized, with a functional dendrites and an axon. [14]

In vivo

A neurite growing in vivo is surrounded by thousands of extracellular signals which in turn can be modulated by hundreds of intracellular pathways, and the mechanisms for how these competing chemical signals effect the ultimate differentiation of neurites in vivo is not precisely understood. It is known that 60% of the time the first neurite that protrudes from the cell body will become the axon. [14] 30% of the time, a neurite not destined to become the axon protrudes from the cell body first. 10% of the time, the neurite that will become the axon protrudes from the cell body simultaneously with one or more other neurites. [14] It has been proposed that a minor neurite could extend outward until it touches an already developed axon of another neuron. At this point, the neurite will begin to differentiate into an axon. This is known as the "touch and go" model. [14] However, this model does not explain how the first axon developed.

Whatever extracellular signals may be involved in inducing axon formation are transduced through at least 4 different pathways: the Rac-1 pathway, the Ras-mediated pathway, the cAMP-liver kinase B1 pathway, and the calcium/calmodulin-dependent protein kinase pathway. [14] A deficiency in any of these pathways would lead to the inability to develop a neuron. [14]

After forming one axon, the neuron must prevent all other neurites from becoming axons as well. This is known as global inhibition. [14] It has been suggested that global inhibition is achieved by a long-range negative feedback signal released from the developed axon and taken up by the other neurite. [15] However, no long range signaling molecule has been discovered. [14] Alternatively, it has been suggested that the buildup of axonal growth factors in the neurite destined to become the axon means there is a depletion of axonal growth factors by default, as they must compete for the same proteins. [16] This causes the other neurites to develop into dendrites as they lack sufficient concentrations of axonal growth factors to become axons. [16] This would allow for a mechanism of global inhibition without the need for a long range signaling molecule.

See also

Related Research Articles

<span class="mw-page-title-main">Axon</span> Long projection on a neuron that conducts signals to other neurons

An axon or nerve fiber is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons, such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired neurological disorders that affect both the peripheral and central neurons. Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. These groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, and Type IV.

<span class="mw-page-title-main">Dendrite</span> Small projection on a neuron that receives signals

A dendrite or dendron is a branched protoplasmic extension of a nerve cell that propagates the electrochemical stimulation received from other neural cells to the cell body, or soma, of the neuron from which the dendrites project. Electrical stimulation is transmitted onto dendrites by upstream neurons via synapses which are located at various points throughout the dendritic tree.

<span class="mw-page-title-main">Neuron</span> Electrically excitable cell found in the nervous system of animals

A neuron, neurone, or nerve cell is an excitable cell that fires electric signals called action potentials across a neural network in the nervous system. Neurons communicate with other cells via synapses, which are specialized connections that commonly use minute amounts of chemical neurotransmitters to pass the electric signal from the presynaptic neuron to the target cell through the synaptic gap.

The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The field of neural development draws on both neuroscience and developmental biology to describe and provide insight into the cellular and molecular mechanisms by which complex nervous systems develop, from nematodes and fruit flies to mammals.

Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogenesis. Synaptogenesis is particularly important during an individual's critical period, during which there is a certain degree of synaptic pruning due to competition for neural growth factors by neurons and synapses. Processes that are not used, or inhibited during their critical period will fail to develop normally later on in life.

<span class="mw-page-title-main">Soma (biology)</span> Portion of a brain cell containing its nucleus

In cellular neuroscience, the soma, perikaryon, neurocyton, or cell body is the bulbous, non-process portion of a neuron or other brain cell type, containing the cell nucleus. Although it is often used to refer to neurons, it can also refer to other cell types as well, including astrocytes, oligodendrocytes, and microglia. There are many different specialized types of neurons, and their sizes vary from as small as about 5 micrometres to over 10 millimetres for some of the smallest and largest neurons of invertebrates, respectively.

Axon guidance is a subfield of neural development concerning the process by which neurons send out axons to reach their correct targets. Axons often follow very precise paths in the nervous system, and how they manage to find their way so accurately is an area of ongoing research.

<span class="mw-page-title-main">Growth cone</span> Large actin extension of a developing neurite seeking its synaptic target

A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target. It is the growth cone that drives axon growth. Their existence was originally proposed by Spanish histologist Santiago Ramón y Cajal based upon stationary images he observed under the microscope. He first described the growth cone based on fixed cells as "a concentration of protoplasm of conical form, endowed with amoeboid movements". Growth cones are situated on the tips of neurites, either dendrites or axons, of the nerve cell. The sensory, motor, integrative, and adaptive functions of growing axons and dendrites are all contained within this specialized structure.

Neuroregeneration involves the regrowth or repair of nervous tissues, cells or cell products. Neuroregenerative mechanisms may include generation of new neurons, glia, axons, myelin, or synapses. Neuroregeneration differs between the peripheral nervous system (PNS) and the central nervous system (CNS) by the functional mechanisms involved, especially in the extent and speed of repair. When an axon is damaged, the distal segment undergoes Wallerian degeneration, losing its myelin sheath. The proximal segment can either die by apoptosis or undergo the chromatolytic reaction, which is an attempt at repair. In the CNS, synaptic stripping occurs as glial foot processes invade the dead synapse.

<span class="mw-page-title-main">Subcommissural organ</span>

The subcommissural organ (SCO) is one of the circumventricular organs of the brain. It is a small glandular structure that is located in the posterior region of the third ventricle, near the entrance of the cerebral aqueduct.

<span class="mw-page-title-main">Glial scar</span> Mass formed in response to injury to the nervous system

A glial scar formation (gliosis) is a reactive cellular process involving astrogliosis that occurs after injury to the central nervous system. As with scarring in other organs and tissues, the glial scar is the body's mechanism to protect and begin the healing process in the nervous system.

<span class="mw-page-title-main">Contactin 1</span> Protein found in humans

Contactin 1, also known as CNTN1, is a protein which in humans is encoded by the CNTN1 gene.

<span class="mw-page-title-main">PTPRM</span> Protein-coding gene in the species Homo sapiens

Receptor-type tyrosine-protein phosphatase mu is an enzyme that in humans is encoded by the PTPRM gene.

Collapsin response mediator protein family or CRMP family consists of five intracellular phosphoproteins of similar molecular size and high (50–70%) amino acid sequence identity. CRMPs are predominantly expressed in the nervous system during development and play important roles in axon formation from neurites and in growth cone guidance and collapse through their interactions with microtubules. Cleaved forms of CRMPs have also been linked to neuron degeneration after trauma induced injury.

<span class="mw-page-title-main">Role of cell adhesions in neural development</span>

Cellular adhesions can be defined as proteins or protein aggregates that form mechanical and chemical linkages between the intracellular and extracellular space. Adhesions serve several critical processes including cell migration, signal transduction, tissue development and repair. Due to this functionality, adhesions and adhesion molecules have been a topic of study within the scientific community. Specifically, it has been found that adhesions are involved in tissue development, plasticity, and memory formation within the central nervous system (CNS), and may prove vital in the generation of CNS-specific therapeutics.

Fasciclin 2 is a 95 kilodalton cell membrane glycoprotein in the immunoglobulin (Ig) – related superfamily of cell adhesion molecules (CAMs). It was first identified in the developing grasshopper embryo, seen dynamically expressed on a subset of fasciculating axons in the central nervous system (CNS), functioning as a neuronal recognition molecule in the regulation of selective axon fasciculation. Subsequently, fasII was cloned and has mainly been studied in the fruit fly. Its extracellular structure consists of two Fibronectin type III domains and five Ig-like C2 domains, having structural homology to the neural cell adhesion molecule (NCAM) found in vertebrates. Alternative splicing of fasII gives rise to its expression in three major isoforms, including a membrane-associated form that is attached to the outer leaflet of the plasma membrane via a glycophosphatidylinositol linkage and two integral transmembrane forms. The larger transmembrane form has an amino acid motif contained in its cytoplasmic domain that is rich in proline, glutamic acid, serine and threonine residues. The fasciclin 1 (Fas1) and fasciclin 3 (Fas3) genes in Drosophila also code for cell adhesion proteins in the nervous system but do not show any structural or functional similarities with NCAM.

<span class="mw-page-title-main">Neuronal self-avoidance</span>

Neuronal self-avoidance, or isoneural avoidance, is an important property of neurons which consists in the tendency of branches arising from a single soma to turn away from one another. The arrangements of branches within neuronal arbors are established during development and result in minimal crossing or overlap as they spread over a territory, resulting in the typical fasciculated morphology of neurons.

N2a cells are a fast-growing mouse neuroblastoma cell line.

<span class="mw-page-title-main">Synaptic stabilization</span> Modifying synaptic strength via cell adhesion molecules

Synaptic stabilization is crucial in the developing and adult nervous systems and is considered a result of the late phase of long-term potentiation (LTP). The mechanism involves strengthening and maintaining active synapses through increased expression of cytoskeletal and extracellular matrix elements and postsynaptic scaffold proteins, while pruning less active ones. For example, cell adhesion molecules (CAMs) play a large role in synaptic maintenance and stabilization. Gerald Edelman discovered CAMs and studied their function during development, which showed CAMs are required for cell migration and the formation of the entire nervous system. In the adult nervous system, CAMs play an integral role in synaptic plasticity relating to learning and memory.

<span class="mw-page-title-main">Neurotubule</span>

Neurotubules are microtubules found in neurons in nervous tissues. Along with neurofilaments and microfilaments, they form the cytoskeleton of neurons. Neurotubules are undivided hollow cylinders that are made up of tubulin protein polymers and arrays parallel to the plasma membrane in neurons. Neurotubules have an outer diameter of about 23 nm and an inner diameter, also known as the central core, of about 12 nm. The wall of the neurotubules is about 5 nm in width. There is a non-opaque clear zone surrounding the neurotubule and it is about 40 nm in diameter. Like microtubules, neurotubules are greatly dynamic and the length of them can be adjusted by polymerization and depolymerization of tubulin.

References

  1. ↑ Flynn, Kevin C (2013-01-01). "The cytoskeleton and neurite initiation". Bioarchitecture. 3 (4): 86–109. doi:10.4161/bioa.26259. ISSN   1949-0992. PMC   4201609 . PMID   24002528.
  2. 1 2 3 Valtorta, F.; Leoni, C. (1999-02-28). "Molecular mechanisms of neurite extension". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 354 (1381): 387–394. doi:10.1098/rstb.1999.0391. ISSN   0962-8436. PMC   1692490 . PMID   10212488.
  3. ↑ Niclou, Simone P.; Franssen, Elske H. P.; Ehlert, Erich M. E.; Taniguchi, Masahiko; Verhaagen, Joost (2003-12-01). "Meningeal cell-derived semaphorin 3A inhibits neurite outgrowth" (PDF). Molecular and Cellular Neurosciences. 24 (4): 902–912. doi:10.1016/s1044-7431(03)00243-4. ISSN   1044-7431. PMID   14697657. S2CID   12637023.
  4. ↑ Luo, Y.; Raible, D.; Raper, J. A. (1993-10-22). "Collapsin: a protein in brain that induces the collapse and paralysis of neuronal growth cones". Cell. 75 (2): 217–227. doi: 10.1016/0092-8674(93)80064-l . ISSN   0092-8674. PMID   8402908. S2CID   46120825.
  5. ↑ Bear, Mark F; Connors, Barry W.; Paradiso, Michael A., Neuroscience, Exploring the Brain, Philadelphia : Lippincott Williams & Wilkins; Third Edition (February 1, 2006). ISBN   0-7817-6003-8
  6. ↑ Qiang, Liang; Yu, Wenqian; Andreadis, Athena; Luo, Minhua; Baas, Peter W. (22 March 2006). "Tau Protects Microtubules in the Axon from Severing by Katanin". The Journal of Neuroscience. 26 (12): 3120–3129. doi:10.1523/JNEUROSCI.5392-05.2006. ISSN   0270-6474. PMC   6674103 . PMID   16554463.
  7. ↑ Xiao, Yangui; Peng, Yinghui; Wan, Jun; Tang, Genyun; Chen, Yuewen; Tang, Jing; Ye, Wen-Cai; Ip, Nancy Y.; Shi, Lei (2013-07-05). "The Atypical Guanine Nucleotide Exchange Factor Dock4 Regulates Neurite Differentiation through Modulation of Rac1 GTPase and Actin Dynamics". Journal of Biological Chemistry. 288 (27): 20034–20045. doi: 10.1074/jbc.M113.458612 . ISSN   0021-9258. PMC   3707701 . PMID   23720743.
  8. ↑ Toriyama, Michinori; Kozawa, Satoshi; Sakumura, Yuichi; Inagaki, Naoyuki (2013-03-18). "Conversion of a signal into forces for axon outgrowth through Pak1-mediated shootin1 phosphorylation". Current Biology. 23 (6): 529–534. Bibcode:2013CBio...23..529T. doi: 10.1016/j.cub.2013.02.017 . hdl: 10061/8621 . ISSN   1879-0445. PMID   23453953.
  9. ↑ Berezin, Vladimir (2009-12-17). Structure and Function of the Neural Cell Adhesion Molecule NCAM. Springer Science & Business Media. ISBN   978-1-4419-1170-4.
  10. ↑ "NeuronJ". imagescience.org. Retrieved 2024-06-10.
  11. ↑ Myatt, Darren R.; Hadlington, Tye; Ascoli, Giorgio A.; Nasuto, Slawomir J. (2012-03-16). "Neuromantic – from Semi-Manual to Semi-Automatic Reconstruction of Neuron Morphology". Frontiers in Neuroinformatics. 6: 4. doi: 10.3389/fninf.2012.00004 . ISSN   1662-5196. PMC   3305991 . PMID   22438842.
  12. ↑ "Neurolucida®". MBF Bioscience. Retrieved 2024-06-10.
  13. ↑ Jones, Peter D.; Molina-Martínez, Beatriz; Niedworok, Anita; Cesare, Paolo (2024). "A microphysiological system for parallelized morphological and electrophysiological read-out of 3D neuronal cell culture". Lab on a Chip. 24 (6): 1750–1761. doi:10.1039/D3LC00963G. ISSN   1473-0197. PMID   38348692.
  14. 1 2 3 4 5 6 7 8 9 10 11 Takano, Tetsuya; Xu, Chundi; Funahashi, Yasuhiro; Namba, Takashi; Kaibuchi, Kozo (2015-06-15). "Neuronal polarization". Development. 142 (12): 2088–2093. doi: 10.1242/dev.114454 . ISSN   0950-1991. PMID   26081570.
  15. ↑ Arimura, Nariko; Kaibuchi, Kozo (2007-03-01). "Neuronal polarity: from extracellular signals to intracellular mechanisms". Nature Reviews Neuroscience. 8 (3): 194–205. doi:10.1038/nrn2056. ISSN   1471-003X. PMID   17311006. S2CID   15556921.
  16. 1 2 Inagaki, Naoyuki; Toriyama, Michinori; Sakumura, Yuichi (2011-06-01). "Systems biology of symmetry breaking during neuronal polarity formation". Developmental Neurobiology. 71 (6): 584–593. doi:10.1002/dneu.20837. hdl: 10061/10669 . ISSN   1932-846X. PMID   21557507. S2CID   14746741.
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