Axon guidance by growth-rate modulation (original) (raw)
Related papers
The growth cone: an integrator of unique cues into refined axon guidance
F1000 biology reports, 2009
One of the challenges to understanding nervous system development is to establish how a fairly limited number of axon guidance cues can set up the patterning of very complex nervous systems. Most of the recent insights relevant to guidance mechanisms have come from cell biologists focusing on processes and molecular machinery controlling the guidance responses in the growth cone.
Axon guidance: A compelling case for repelling growth cones
Cell, 1995
The guidance of axons to their targets represents a key stage in the assembly of the nervous system, linking the early inductive interactions that establish neuronal identity to the later steps of synapse formation. Neurons are required to extend axons through a variety of cellular environments, and the task of perceiving, integrating, and responding to the myriad signals present in the immediate vicinity of the axon falls to the growth cone, a sensory and motor apparatus located at the distal tip of the developing axon. Attempts to unravel the mechanisms of axonal guidance have centered on four main issues: the cellular strategies used to influence the rate of extension and the orientation of growth cones; the nature of molecules in the local environment of the axon that control growth cone behavior; the identity of receptors on the surface of growth cones that respond to these guidance cues; and the intracellular machinery that integrates multiple extracellular signals to produce the coordinated and directed response of growth cone navigation.
A model for axon guidance: Sensing, transduction and movement
AIP Conference Proceedings, 2008
Axon guidance by graded diffusible ligands plays a crucial role in the developing nervous system. In this paper, we extend the mathematical description of the growth cone transduction cascade of [2] by adding a model of the gradient sensing process related to the theory of [6]. The resulting model is composed by a series of subsystems characterized by suitable input/output relations. The study of the transmission of the noise-to-signal ratio allows to predict the variability of the gradient assay as a function of experimental parameters as the ligand concentration, both in the single and in the multiple ligand tests. For this latter condition, we address the biologically relevant case of silencing in commissural axons. We also consider a phenomenological model which reproduces the results of the experiments of [32]. This simple model allows to test hypotheses on receptor functions and regulation in time. 2000 Mathematics Subject Classification. 92B05 and 60G35 and 65N30. Key words and phrases. Growth cone pathfinding and Commissural axons and Chemotaxis and Gradient sensing and Mathematical model and Computational model.
Molecular Biology of Axon Guidance
Neuron, 1996
Neuronal growth cones navigate over long distances along specific pathways to find their correct targets. The mechanisms and molecules that direct this pathfinding are the topics of this review. Growth cones appear to be guided by at least four different mechanisms: contact attraction, chemoattraction, contact repulsion, and chemorepulsion. Evidence is accumulating that these mechanisms act simultaneously and in a coordinated manner to direct pathfinding and that they are mediated by mechanistically and evolutionarily conserved ligand-receptor systems.
A Multiscale Computational Model of Chemotactic Axon Guidance
International Journal of Computational Models and Algorithms in Medicine, 2012
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...
Directional guidance of nerve growth cones
Current Opinion in Neurobiology, 2006
The intricate connections of the nervous system are established, in part, by elongating axonal fibers that are directed by complex guidance systems to home in on their specific targets. The growth cone, the major motile apparatus at the tip of axons, explores its surroundings and steers the axon along a defined path to its appropriate target. Significant progress has been made in identifying the guidance molecules and receptors that regulate growth cone pathfinding, the signaling cascades underlying distinct growth cone behaviors, and the cytoskeletal components that give rise to the directional motility of the growth cone. Recent studies have also shed light on the sophisticated mechanisms and new players utilized by the growth cone during pathfinding. It is clear that axon pathfinding requires a growth cone to sample and integrate various signals both in space and in time, and subsequently to coordinate the dynamics of its membrane, cytoskeleton and adhesion to generate specific responses.
Axon guidance: A balance of signals sets axons on the right track
Current Biology, 1999
Axon guidance depends on the transduction of extracellular guidance cues into motile responses by the axonal growth cone. Recent studies in vivo have elucidated mechanisms required for this process that involve kinases and phosphatases, calcium dynamics and remodeling of the actin cytoskeleton.
Cyclic nucleotide-dependent switching of mammalian axon guidance depends on gradient steepness
Molecular and Cellular Neuroscience, 2011
Correct wiring of the nervous system during development requires axons to respond appropriately to gradients of attractive and repulsive guidance cues. However, the steepness and concentration of these gradients vary in vivo, for instance, with distance from the target. Understanding how these changing conditions affect the navigation strategies used by developing axons is important for understanding how they are guided over long distances. Previous work has shown that cyclic nucleotide levels determine whether axons are attracted or repelled by steep gradients of the same guidance cue, but it is unknown whether this is also true for shallow gradients. We therefore investigated the guidance responses of rat superior cervical ganglion (SCG) axons in both steep and shallow gradients of nerve growth factor (NGF). In steep gradients we found that cyclic nucleotide-dependent switching occurred, consistent with previous reports. Surprisingly however, we found that in shallow NGF gradients, cyclic nucleotide-dependent switching did not occur. These results suggest that there may be substantial differences in the way axons respond to gradient-based guidance cues depending on where they are within the gradient.
ABSTRACTMyosin II (MII) activity is required for elongating mammalian sensory axons to change speed and direction in response to Nerve Growth Factor (NGF) and laminin-1 (LN). NGF signaling induces faster outgrowth on LN through regulation of actomyosin restraint of microtubule advance into the growth cone periphery. It remains unclear whether growth cone turning on LN works through the same mechanism and, if it does, how the mechanism produces directed advance. Using a novel method for substrate patterning, we tested how directed advance occurs on LN by creating a gap immediately in front of a growth cone advancing on a narrow LN path. The growth cone stopped until an actin-rich protrusion extended over the gap, adhered to LN, and became stabilized. Stepwise advance over the gap was triggered by microtubule +tip entry up to the adhesion site of the protrusion and was independent of traction force pulling. We found that the probability of microtubule entry is regulated at the level o...
Axon guidance: asymmetric signaling orients polarized outgrowth
Trends in Cell Biology, 2008
A network of connections is established as neural circuits form between neurons. To make these connections, neurons initiate asymmetric axon outgrowth in response to extracellular guidance cues. Within the specialized growth cones of migrating axons, F-actin and microtubules asymmetrically accumulate where an axon projects forward. Although many guidance cues, receptors, and intracellular signaling components required for axon guidance have been identified, the means through which the asymmetry is established and maintained is unclear. We discuss recent studies in invertebrate and vertebrate organisms that define a signaling module comprising UNC-6(netrin), UNC-40(DCC), PI3K, Rac, and MIG-10(lamellipodin) and we consider how this module could establish polarized outgrowth in response to guidance cues.