A Multiscale Computational Model of Chemotactic Axon Guidance

2012 ◽  
Vol 3 (4) ◽  
pp. 43-60
Author(s):  
Giacomo Aletti ◽  
Paola Causin ◽  
Giovanni Naldi ◽  
Matteo Semplice
Keyword(s):  
Mathematical Model ◽  
Nervous System ◽  
Axon Guidance ◽  
Growth Cone ◽  
Distal Part ◽  
Transmembrane Receptors ◽  
Axonal Projections ◽  
Long Time ◽  
Tight Connection ◽  
Cytoskeleton Rearrangement

In the development of the nervous system, the migration of neurons driven by chemotactic cues has been known since a long time to play a key role. In this mechanism, the axonal projections of neurons detect very small differences in extracellular ligand concentration across the tiny section of their distal part, the growth cone. The internal transduction of the signal performed by the growth cone leads to cytoskeleton rearrangement and biased cell motility. A mathematical model of neuron migration provides hints of the nature of this process, which is only partially known to biologists and is characterized by a complex coupling of microscopic and macroscopic phenomena. This chapter focuses on the tight connection between growth cone directional sensing as the result of the information collected by several transmembrane receptors, a microscopic phenomenon, and its motility, a macroscopic outcome. The biophysical hypothesis investigated is the role played by the biased re-localization of ligand-bound receptors on the membrane, actively convected by growing microtubules. The results of the numerical simulations quantify the positive feedback exerted by the receptor redistribution, assessing its importance in the neural guidance mechanism.

A Multiscale Computational Model of Chemotactic Axon Guidance

2011 ◽  
pp. 628-645
Author(s):  
Giacomo Aletti ◽  
Paola Causin ◽  
Giovanni Naldi ◽  
Matteo Semplice
Keyword(s):  
Mathematical Model ◽  
Nervous System ◽  
Cell Motility ◽  
Growth Cone ◽  
Ligand Concentration ◽  
Transmembrane Receptors ◽  
Axonal Projections ◽  
Long Time ◽  
Tight Connection ◽  
Cytoskeleton Rearrangement

In the development of the nervous system, the migration of neurons driven by chemotactic cues has been known since a long time to play a key role. In this mechanism, the axonal projections of neurons detect very small differences in extracellular ligand concentration across the tiny section of their distal part, the growth cone. The internal transduction of the signal performed by the growth cone leads to cytoskeleton rearrangement and biased cell motility. A mathematical model of neuron migration provides hints of the nature of this process, which is only partially known to biologists and is characterized by a complex coupling of microscopic and macroscopic phenomena. This chapter focuses on the tight connection between growth cone directional sensing as the result of the information collected by several transmembrane receptors, a microscopic phenomenon, and its motility, a macroscopic outcome. The biophysical hypothesis investigated is the role played by the biased re-localization of ligand-bound receptors on the membrane, actively convected by growing microtubules. The results of the numerical simulations quantify the positive feedback exerted by the receptor redistribution, assessing its importance in the neural guidance mechanism.

scholarly journals A mathematical model explains saturating axon guidance responses to molecular gradients

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Huyen Nguyen ◽  
Peter Dayan ◽  
Zac Pujic ◽  
Justin Cooper-White ◽  
Geoffrey J Goodhill
Keyword(s):  
Mathematical Model ◽  
Nervous System ◽  
Axon Guidance ◽  
Predictive Model ◽  
Growth Cone ◽  
Growth Cones ◽  
Mathematical Explanation ◽  
In Vitro Growth

Correct wiring is crucial for the proper functioning of the nervous system. Molecular gradients provide critical signals to guide growth cones, which are the motile tips of developing axons, to their targets. However, in vitro, growth cones trace highly stochastic trajectories, and exactly how molecular gradients bias their movement is unclear. Here, we introduce a mathematical model based on persistence, bias, and noise to describe this behaviour, constrained directly by measurements of the detailed statistics of growth cone movements in both attractive and repulsive gradients in a microfluidic device. This model provides a mathematical explanation for why average axon turning angles in gradients in vitro saturate very rapidly with time at relatively small values. This work introduces the most accurate predictive model of growth cone trajectories to date, and deepens our understanding of axon guidance events both in vitro and in vivo.

scholarly journals A Subtle Network Mediating Axon Guidance: Intrinsic Dynamic Structure of Growth Cone, Attractive and Repulsive Molecular Cues, and the Intermediate Role of Signaling Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-26 ◽  
Author(s):  
Xiyue Ye ◽  
Yan Qiu ◽  
Yuqing Gao ◽  
Dong Wan ◽  
Huifeng Zhu
Keyword(s):  
Axon Guidance ◽  
Signaling Pathways ◽  
Growth Cone ◽  
System Development ◽  
Dynamic Structure ◽  
Nervous System Development ◽  
Axonal Projections ◽  
Directional Decisions ◽  
Intrinsic Dynamic

A fundamental feature of both early nervous system development and axon regeneration is the guidance of axonal projections to their targets in order to assemble neural circuits that control behavior. In the navigation process where the nerves grow toward their targets, the growth cones, which locate at the tips of axons, sense the environment surrounding them, including varies of attractive or repulsive molecular cues, then make directional decisions to adjust their navigation journey. The turning ability of a growth cone largely depends on its highly dynamic skeleton, where actin filaments and microtubules play a very important role in its motility. In this review, we summarize some possible mechanisms underlying growth cone motility, relevant molecular cues, and signaling pathways in axon guidance of previous studies and discuss some questions regarding directions for further studies.

scholarly journals Semaphorins in axon regeneration: developmental guidance molecules gone wrong?

2006 ◽  
Vol 361 (1473) ◽  
pp. 1499-1511 ◽  
Author(s):  
R. Jeroen Pasterkamp ◽  
Joost Verhaagen
Keyword(s):  
Signal Transduction ◽  
Nervous System ◽  
Axon Guidance ◽  
Growth Cone ◽  
Axon Regeneration ◽  
Critical Role ◽  
Developmental Guidance ◽  
Receptor Complexes ◽  
Fibrotic Scar ◽  
Intracellular Signal

Semaphorins are developmental axon guidance cues that continue to be expressed during adulthood and are regulated by neural injury. During the formation of the nervous system, repulsive semaphorins guide axons to their targets by restricting and channelling their growth. They affect the growth cone cytoskeleton through interactions with receptor complexes that are linked to a complicated intracellular signal transduction network. Following injury, regenerating axons stop growing when they reach the border of the glial-fibrotic scar, in part because they encounter a potent molecular barrier that inhibits growth cone extension. A number of secreted semaphorins are expressed in the glial-fibrotic scar and at least one transmembrane semaphorin is upregulated in oligodendrocytes surrounding the lesion site. Semaphorin receptors, and many of the signal transduction components required for semaphorin signalling, are present in injured central nervous system neurons. Here, we review evidence that supports a critical role for semaphorin signalling in axon regeneration, and highlight a number of challenges that lie ahead with respect to advancing our understanding of semaphorin function in the normal and injured adult nervous system.

The metalloproteinase ADAM10 is required for retinal ganglion cell axon guidance in the developing visual systems

2007 ◽  
Vol 30 (4) ◽  
pp. 77
Author(s):  
Y. Y. Chen ◽  
C. L. Hehr ◽  
K. Atkinson-Leadbeater ◽  
J. C. Hocking ◽  
S. McFarlane
Keyword(s):  
Ganglion Cell ◽  
Axon Guidance ◽  
Retinal Ganglion Cell ◽  
Growth Cone ◽  
Expression Patterns ◽  
Optic Tract ◽  
Axon Growth ◽  
Proteolytic Processing ◽  
Retinal Ganglion

Background: The growth cone interprets cues in its environment in order to reach its target. We want to identify molecules that regulate growth cone behaviour in the developing embryo. We investigated the role of A disintegrin and metalloproteinase 10 (ADAM10) in axon guidance in the developing visual system of African frog, Xenopus laevis. Methods: We first examined the expression patterns of adam10 mRNA by in situ hybridization. We then exposed the developing optic tract to an ADAM10 inhibitor, GI254023X, in vivo. Lastly, we inhibited ADAM10 function in diencephalic neuroepithelial cells (through which retinal ganglion cell (RGC) axons extend) or RGCs by electroporating or transfecting an ADAM10 dominant negative (dn-adam10). Results: We show that adam10 mRNA is expressed in the dorsal neuroepithelium over the time RGC axons extend towards their target, the optic tectum. Second, pharmacological inhibition of ADAM10 in an in vivo exposed brain preparation causes the failure of RGC axons to recognize their target at low concentrations (0.5, 1 μM), and the failure of the axons to make a caudal turn in the mid-diencephalon at higher concentration (5 μM). Thus, ADAM10 function is required for RGC axon guidance at two key guidance decisions. Finally, molecular inhibition of ADAM10 function by electroporating dn-adam10 in the brain neuroepithelium causes defects in RGC axon target recognition (57%) and/or defects in caudal turn (12%), as seen with the pharmacological inhibitor. In contrast, molecular inhibition of ADAM10 within the RGC axons has no effect. Conclusions: These data argue strongly that ADAM10 acts cell non-autonomously within the neuroepithelium to regulate the guidance of RGC axons. This study shows for the first time that a metalloproteinase acts in a cell non-autonomous fashion to direct vertebrate axon growth. It will provide important insights into candidate molecules that could be used to reform nerve connections if destroyed because of injury or disease. References Hattori M, Osterfield M, Flanagan JG. Regulated cleavage of a contact-mediated axon repellent. Science 2000; 289(5483):1360-5. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB. Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell 2005; 123(2):291-304. Pan D, Rubin GM. Kuzbanian controls proteolytic processing of Notch and mediates lateral inhibition during Drosophila and vertebrate neurogenesis. Cell 1997; 90(2):271-80.

Acid-Sensing Ion Channels

2020 ◽  
Author(s):  
Stefan Gründer
Keyword(s):  
Nervous System ◽  
Ion Channels ◽  
Excitatory Synapses ◽  
Detailed Characterization ◽  
High Affinity ◽  
Acid Sensing Ion Channels ◽  
Long Time ◽  
Pathological Pain

Acid-sensing ion channels (ASICs) are proton-gated Na+ channels. Being almost ubiquitously present in neurons of the vertebrate nervous system, their precise function remained obscure for a long time. Various animal toxins that bind to ASICs with high affinity and specificity have been tremendously helpful in uncovering the role of ASICs. We now know that they contribute to synaptic transmission at excitatory synapses as well as to sensing metabolic acidosis and nociception. Moreover, detailed characterization of mouse models uncovered an unanticipated role of ASICs in disorders of the nervous system like stroke, multiple sclerosis, and pathological pain. This review provides an overview on the expression, structure, and pharmacology of ASICs plus a summary of what is known and what is still unknown about their physiological functions and their roles in diseases.

Research on cargo-loading optimization based on genetic and fuzzy integration

2021 ◽  
Vol 40 (4) ◽  
pp. 8493-8500
Author(s):  
Yanwei Du ◽  
Feng Chen ◽  
Xiaoyi Fan ◽  
Lei Zhang ◽  
Henggang Liang
Keyword(s):  
Genetic Algorithm ◽  
Mathematical Model ◽  
Three Dimensional ◽  
Distribution Center ◽  
Long Time ◽  
Low Efficiency ◽  
Decision Making Model ◽  
The Mathematical Model ◽  
Loading Scheme

With the increase of the number of loaded goods, the number of optional loading schemes will increase exponentially. It is a long time and low efficiency to determine the loading scheme with experience. Genetic algorithm is a search heuristic algorithm used to solve optimization in the field of computer science artificial intelligence. Genetic algorithm can effectively select the optimal loading scheme but unable to utilize weight and volume capacity of cargo and truck. In this paper, we propose hybrid Genetic and fuzzy logic based cargo-loading decision making model that focus on achieving maximum profit with maximum utilization of weight and volume capacity of cargo and truck. In this paper, first of all, the components of the problem of goods stowage in the distribution center are analyzed systematically, which lays the foundation for the reasonable classification of the problem of goods stowage and the establishment of the mathematical model of the problem of goods stowage. Secondly, the paper abstracts and defines the problem of goods loading in distribution center, establishes the mathematical model for the optimization of single car three-dimensional goods loading, and designs the genetic algorithm for solving the model. Finally, Matlab is used to solve the optimization model of cargo loading, and the good performance of the algorithm is verified by an example. From the performance evaluation analysis, proposed the hybrid system achieve better outcomes than the standard SA model, GA method, and TS strategy.

scholarly journals Murine Esophagus Expresses Glial-Derived Central Nervous System Antigens

2021 ◽  
Vol 22 (6) ◽  
pp. 3233
Author(s):  
Christopher Kapitza ◽  
Rittika Chunder ◽  
Anja Scheller ◽  
Katherine S. Given ◽  
Wendy B. Macklin ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Schwann Cells ◽  
Glial Cells ◽  
Proteolipid Protein ◽  
Pcr Analysis ◽  
Specific Expression ◽  
Enteric Glial Cells ◽  
Cell Type Specific Expression ◽  
Long Time

Multiple sclerosis (MS) has been considered to specifically affect the central nervous system (CNS) for a long time. As autonomic dysfunction including dysphagia can occur as accompanying phenomena in patients, the enteric nervous system has been attracting increasing attention over the past years. The aim of this study was to identify glial and myelin markers as potential target structures for autoimmune processes in the esophagus. RT-PCR analysis revealed glial fibrillary acidic protein (GFAP), proteolipid protein (PLP), and myelin basic protein (MBP) expression, but an absence of myelin oligodendrocyte glycoprotein (MOG) in the murine esophagus. Selected immunohistochemistry for GFAP, PLP, and MBP including transgenic mice with cell-type specific expression of PLP and GFAP supported these results by detection of (1) GFAP, PLP, and MBP in Schwann cells in skeletal muscle and esophagus; (2) GFAP, PLP, but no MBP in perisynaptic Schwann cells of skeletal and esophageal motor endplates; (3) GFAP and PLP, but no MBP in glial cells surrounding esophageal myenteric neurons; and (4) PLP, but no GFAP and MBP in enteric glial cells forming a network in the esophagus. Our results pave the way for further investigations regarding the involvement of esophageal glial cells in the pathogenesis of dysphagia in MS.

scholarly journals Axon Guidance: Opposing EPHects in the Growth Cone

Cell ◽  
2005 ◽  
Vol 121 (1) ◽  
pp. 4-6 ◽  
Author(s):  
Rüdiger Klein
Keyword(s):  
Axon Guidance ◽  
Growth Cone
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