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Current Opinion in Neurobiology Aug 2020Upon receiving injury signals, neurons can activate various pathways to reduce harm, initiate neuroprotection, and repair damaged neurite without cell death. Here, we... (Review)
Review
Upon receiving injury signals, neurons can activate various pathways to reduce harm, initiate neuroprotection, and repair damaged neurite without cell death. Here, we review recent progresses in the study of neurite repair focusing on neuronal cell-autonomous mechanisms, including new findings on ion channels that serve as key regulators to initiate neurite repair and intrinsic signaling pathways and transcriptional and post-transcriptional factors that facilitate neurite repair. We also touch upon reports on how dendrites may be affected upon axotomy and how the regeneration potential in injured neurites might be maximized.
Topics: Axotomy; Nerve Regeneration; Neurites; Neurons
PubMed: 32278210
DOI: 10.1016/j.conb.2020.02.010 -
Biomechanics and Modeling in... Feb 2022The establishment of a functioning neuronal network is a crucial step in neural development. During this process, neurons extend neurites-axons and dendrites-to meet... (Review)
Review
The establishment of a functioning neuronal network is a crucial step in neural development. During this process, neurons extend neurites-axons and dendrites-to meet other neurons and interconnect. Therefore, these neurites need to migrate, grow, branch and find the correct path to their target by processing sensory cues from their environment. These processes rely on many coupled biophysical effects including elasticity, viscosity, growth, active forces, chemical signaling, adhesion and cellular transport. Mathematical models offer a direct way to test hypotheses and understand the underlying mechanisms responsible for neuron development. Here, we critically review the main models of neurite growth and morphogenesis from a mathematical viewpoint. We present different models for growth, guidance and morphogenesis, with a particular emphasis on mechanics and mechanisms, and on simple mathematical models that can be partially treated analytically.
Topics: Axons; Models, Theoretical; Morphogenesis; Neurites; Neurons
PubMed: 34994872
DOI: 10.1007/s10237-021-01539-0 -
Cellular and Molecular Life Sciences :... Jan 2015The precise wiring of the nervous system is a combined outcome of progressive and regressive events during development. Axon guidance and synapse formation intertwined... (Review)
Review
The precise wiring of the nervous system is a combined outcome of progressive and regressive events during development. Axon guidance and synapse formation intertwined with cell death and neurite pruning sculpt the mature circuitry. It is now well recognized that pruning of dendrites and axons as means to refine neuronal networks, is a wide spread phenomena required for the normal development of vertebrate and invertebrate nervous systems. Here we will review the arising principles of cellular and molecular mechanisms of neurite pruning. We will discuss these principles in light of studies in multiple neuronal systems, and speculate on potential explanations for the emergence of neurite pruning as a mechanism to sculpt the nervous system.
Topics: Animals; Humans; Nerve Net; Neural Pathways; Neurites; Neurogenesis; Signal Transduction; Synapses
PubMed: 25213356
DOI: 10.1007/s00018-014-1729-6 -
Cell and Tissue Research Jan 2015The formation of a neurite, the basis for axons and dendrites, begins with the concerted accumulation and organization of actin and microtubules. Whereas much is known... (Review)
Review
The formation of a neurite, the basis for axons and dendrites, begins with the concerted accumulation and organization of actin and microtubules. Whereas much is known about the proteins that play a role in these processes, because they perform similar functions in axon branching and filopodia formation, much remains to be discovered concerning the interaction of these individual cytoskeletal regulators during neurite formation. Here, we review the literature regarding various models of filopodial formation and the way in which proteins that control actin organization and polymerization induce neurite formation. Although several different regulators of actin polymerization are involved in neurite initiation, redundancy occurs between these regulators, as the effects of the loss of a single regulator can be mitigated by the addition of neurite-promoting substrates and proteins. Similar to actin dynamics, both microtubule stabilizing and destabilizing proteins play a role in neurite initiation. Furthermore, interactions between the actin and microtubule cytoskeleton are required for neurite formation. Several lines of evidence indicate that the interactions between these two components of the cytoskeleton are needed for force generation and for the localization of microtubules at sites of nascent neurites. The general theme that emerges is the existence of several central regulatory pathways on which extracellular cues converge to control and organize both actin and microtubules to induce the formation of neurites.
Topics: Actins; Animals; Cytoskeleton; Humans; Microtubules; Models, Biological; Neurites; Signal Transduction
PubMed: 25080065
DOI: 10.1007/s00441-014-1955-0 -
Molecular Neurobiology Feb 2022The extracellular matrix (ECM) plays a critical role in development, homeostasis, and regeneration of tissue structures and functions. Cell interactions with the ECM are...
The extracellular matrix (ECM) plays a critical role in development, homeostasis, and regeneration of tissue structures and functions. Cell interactions with the ECM are dynamic and cells respond to ECM remodeling by changes in morphology and motility. During nerve regeneration, the ECM facilitates neurite outgrowth and guides axons with target specificity. Decellularized ECMs retain structural, biochemical, and biomechanical cues of native ECM and have the potential to replace damaged matrix to support cell activities during tissue repair. To determine the ECM components that contribute to nerve regeneration, we analyzed neuron-ECM interactions on two types of decellularized ECM. One matrix was composed primarily of fibronectin (FN) fibrils, and the other FN-rich ECM also contained significant numbers of type I collagen (COL I) fibrils. Using primary neurons dissociated from superior cervical ganglion (SCG) explants, we found that neurites were extended on both matrices without a significant difference in average neurite length after 24 h. The most distinctive features of neurites on the FN matrix were numerous short actin-filled protrusions and longer branches extending from neurite shafts. Very few protrusions and branches were detected on FN-COL matrix. Growth cone morphologies also differed with mostly filopodial growth cones on FN matrix whereas on FN-COL matrix, equivalent numbers of filopodial and slender growth cones were formed. Our work provides new information about how changes in major components of the ECM during tissue repair modulate neuron and growth cone morphologies and helps to define the contributions of neuron-ECM interactions to nerve development and regeneration.
Topics: Cells, Cultured; Collagen; Decellularized Extracellular Matrix; Extracellular Matrix; Fibronectins; Growth Cones; Neurites; Neuronal Outgrowth
PubMed: 34845592
DOI: 10.1007/s12035-021-02637-x -
Journal of Genetics and Genomics = Yi... Apr 2019Dendrites and axons are delicate neuronal membrane extensions that undergo degeneration after physical injuries. In neurodegenerative diseases, they often degenerate... (Review)
Review
Dendrites and axons are delicate neuronal membrane extensions that undergo degeneration after physical injuries. In neurodegenerative diseases, they often degenerate prior to neuronal death. Understanding the mechanisms of neurite degeneration has been an intense focus of neurobiology research in the last two decades. As a result, many discoveries have been made in the molecular pathways that lead to neurite degeneration and the cell-cell interactions responsible for the subsequent clearance of neuronal debris. Drosophila melanogaster has served as a prime in vivo model system for identifying and characterizing the key molecular players in neurite degeneration, thanks to its genetic tractability and easy access to its nervous system. The knowledge learned in the fly provided targets and fuel for studies in other model systems that have further enhanced our understanding of neurodegeneration. In this review, we will introduce the experimental systems developed in Drosophila to investigate injury-induced neurite degeneration, and then discuss the biological pathways that drive degeneration. We will also cover what is known about the mechanisms of how phagocytes recognize and clear degenerating neurites, and how recent findings in this area enhance our understanding of neurodegenerative disease pathology.
Topics: Animals; Drosophila melanogaster; Humans; Neurites; Neurodegenerative Diseases
PubMed: 31080046
DOI: 10.1016/j.jgg.2019.03.010 -
Cancer Science Sep 2007Wnt signaling consists of a highly conserved set of biochemical pathways that have a multitude of functions during embryonic development and in the adult. The Wnt... (Review)
Review
Wnt signaling consists of a highly conserved set of biochemical pathways that have a multitude of functions during embryonic development and in the adult. The Wnt proteins are extracellular agents that often act as gradient morphogens, indicating that their distribution in tissues is tightly controlled. This attribute is also characteristic of factors that regulate neurite outgrowth and guide axons precisely to their specific destinations. Several studies in various species now have established that Wnts and their receptors have an important role in axonal guidance. Different ligand/receptor combinations have been identified that mediate this activity in many of the experimental models. Clues about downstream effector molecules have come from in vitro systems. In this article, the authors review the results from many of these models, evaluate what is known about the associated signaling pathways and speculate about the direction of future research.
Topics: Animals; Cell Proliferation; Humans; Neurites; Neurons; Signal Transduction; Wnt Proteins
PubMed: 17627619
DOI: 10.1111/j.1349-7006.2007.00536.x -
Current Opinion in Neurobiology Dec 2013Injury to mature neurites triggers a series of events that have both growth promoting and inhibitory roles. Recent evidence from a variety of experimental models has... (Review)
Review
Injury to mature neurites triggers a series of events that have both growth promoting and inhibitory roles. Recent evidence from a variety of experimental models has revealed new neuronal re-growth modulators. The action of these modulators must be precisely regulated both in time and space, and involves multiple cellular processes including retrograde signaling and local translation in the injured neurite. New genetic techniques, in combination with pharmacological approaches, have served to advance mechanistic dissection of neuronal response to injury. Better understanding of the spatio-temporal cues would greatly aid in the development of effective regenerative therapies.
Topics: Animals; Humans; MAP Kinase Kinase Kinases; Microtubules; Nerve Regeneration; Neurites; Signal Transduction
PubMed: 23856616
DOI: 10.1016/j.conb.2013.06.009 -
Cells Jul 2021Neurogenesis and functional brain activity require complex associations of inherently programmed secretory elements that are regulated precisely and temporally. Family...
Neurogenesis and functional brain activity require complex associations of inherently programmed secretory elements that are regulated precisely and temporally. Family with sequence similarity 19 A1 (FAM19A1) is a secreted protein primarily expressed in subsets of terminally differentiated neuronal precursor cells and fully mature neurons in specific brain substructures. Several recent studies have demonstrated the importance of FAM19A1 in brain physiology; however, additional information is needed to support its role in neuronal maturation and function. In this study, dendritic spine morphology in -ablated mice and neurite development during in vitro neurogenesis were examined to understand the putative role of FAM19A1 in neural integrity. Adult -deficient mice showed low dendritic spine density and maturity with reduced dendrite complexity compared to wild-type (WT) littermates. To further explore the effect of FAM19A1 on neuronal maturation, the neurite outgrowth pattern in primary neurons was analyzed in vitro with and without FAM19A1. In response to FAM19A1, WT primary neurons showed reduced neurite complexity, whereas -decifient primary neurons exhibited increased neurite arborization, which was reversed by supplementation with recombinant FAM19A1. Together, these findings suggest that FAM19A1 participates in dendritic spine development and neurite arborization.
Topics: Age Factors; Animals; Brain; Cells, Cultured; Chemokines; Dendritic Spines; Female; Gestational Age; Male; Mice, Inbred C57BL; Mice, Knockout; Neurites; Neuronal Outgrowth; Pregnancy; Signal Transduction; Mice
PubMed: 34440636
DOI: 10.3390/cells10081868 -
Scientific Reports Feb 2023Caldendrin is a Ca binding protein that interacts with multiple effectors, such as the Ca1 L-type Ca channel, which play a prominent role in regulating the outgrowth of...
Caldendrin is a Ca binding protein that interacts with multiple effectors, such as the Ca1 L-type Ca channel, which play a prominent role in regulating the outgrowth of dendrites and axons (i.e., neurites) during development and in response to injury. Here, we investigated the role of caldendrin in Ca1-dependent pathways that impinge upon neurite growth in dorsal root ganglion neurons (DRGNs). By immunofluorescence, caldendrin was localized in medium- and large- diameter DRGNs. Compared to DRGNs cultured from WT mice, DRGNs of caldendrin knockout (KO) mice exhibited enhanced neurite regeneration and outgrowth. Strong depolarization, which normally represses neurite growth through activation of Ca1 channels, had no effect on neurite growth in DRGN cultures from female caldendrin KO mice. Remarkably, DRGNs from caldendrin KO males were no different from those of WT males in terms of depolarization-dependent neurite growth repression. We conclude that caldendrin opposes neurite regeneration and growth, and this involves coupling of Ca1 channels to growth-inhibitory pathways in DRGNs of females but not males.
Topics: Female; Mice; Animals; Neurites; Ganglia, Spinal; Neurons; Axons; Nerve Regeneration; Cells, Cultured
PubMed: 36788334
DOI: 10.1038/s41598-023-29622-9