Talk:Axon guidance

Reference
For a reference, I found this fairly detailed page, but I'm not wiki-savvy enough to cite it properly.

Hi
Hi Is Axon Guidance a biology or physics problem? Is there any way that you could class it as phyiscs becuase of the methods people use to try to solve it (eg large compter models)?

I know this is a weird question but its been listed on the unsolved problems in physics page

Thanks

CaptinJohn 10:52, 13 November 2007 (UTC)

I think it's MAINLY a biology problem because it's about a biological system (cells in the nervous system etc.) There have been efforts to elucidate the mechanisms and pathways involved in this process by physicists and informaticians as well. They construct models and exemplary systems to analyse the issue. Maybe that's why it is an "unsolved problem in physics": They think about it, too! :) --91.10.240.37 (talk) 17:47, 9 February 2008 (UTC)

Removed content
To begin, neurons, after differentiation, start to express axons towards targets. They originate specific to specific (pathfinding). Within this, pruning of axons occurs to create better connections, essentially correcting mistakes, as they interact with this complex environment. As stated, growth of an axon occurs predominantly at the growth cone. The bulbous ends of axons act as a battering ram that adapts and grows through fasciculation and defasiculation. Even if the end of an axon is cut, the growth cone will continue to extend. The shape of the growth cone is very dependent on the context. In elongation, the growth cone is moving fast and will look stretched out. At a choice point, the growth cone will split and move along different fasicle. When the growth cone reaches the target, the growth cone will embed and slow down. In all of these contexts, the growth cone’s shape is dependent on the filopodia guiding the movement. The structure of the growth cone of an axon is very dynamic (always sensing the environment: extending and retracting). The signaling molecules will determine extension or retraction of each filipodia. The filopodial movement is driven by actin polymerization and depolymerization. Extension will be actin polymerization and retraction will be actin depolymerization. Tubulin acts as the bigger motor for the whole axon to pull from the myosin anchored to tubulin. Growth cones use tension between themselves and the substrate to move. Actin is linked to the substrate like a clutch. Myosin pulls body of growth cone forward to release the clutch. The filopodium, now free, can use actin polymerization to move forward and engage a new clutch on the substrate. This cycle continues to allow for growth of the axon due to axonal transport of supplies for growth and the recycling of cargo back into the nucleus to create new supplies for more polymerization.

Growth cone guidance is done through the interaction between actin and microtubules. The balance of stability can be influenced by guidance molecules that can stabilize or destabilize actin and microtubules. Stabilization will steer the cone in that specific direction with destabilization turning the growth cone in the other. There are two main types of guidance molecules: long range (secreted) and short range (contact-mediated). Both of these types contain attractants and repulsions. Different contexts lead to different “stiffness” of tissues, which gives specificity to neuronal axonal pathfinding in addition to the guidance cues. The canonical (his canonical) guidance cues are netrins, slits, semaphorins, and ephrins. It is a lot more complicated than just saying one type is attractive and the other is repulsive. These molecules are context-dependent and dynamically complex. The molecules effectively make a “path” for the axon to follow through differences in adhesion strength. Some molecules, like NCAM, control the defasiculation of nerves. This process has to be tightly controlled for the correct formation of bundles and crossing of axons that need defasiculation and refasiculation to branch and grow. There are different forms of cues that regulate the elongation (II) or cross (I). Chemotaxis is a good example of a type of axonal guidance. Nerve growth factor is a classical chemoattractant where axons grow towards NGF all the time. The opposite of that is semaphorin. If released in the extracellular space, the axon will grow away from semaphorin. Another classic attractant is netrin. Netrin is the major molecule involved in the directed growth of axons towards the neural floorplate. When knocked out, abnormal migration of neurons occurs. Semaphorin, again, is a chemo-repulsive molecule. It acts by inducing collapse of growth cones. However, this repulsion can be switched and display attractive qualities if the growth cone contains elevated levels of cGMP. Adhesive and chemotactic forces work together to promote axon guidance. This can be seen very well in the cues for retinal ganglion neurons guidance to the tectum. It starts with contact adhesion with laminin along the retina, but then the addition of onh switches the adhesion to repulsive. This bumps the axons through an attractive gradient of netrin-1 towards the optic chiasm. Here, the axons containing the F receptor for Ephrin B stay on ipsilateral side while no receptor crosses through contact mediated adhesion up the optic tract. There is some repulsiveness from semaphorins to keep the axons lateral. Before the tectum, a gradient of FGF is there to slow the axon down. There is a gradient of ephrin A in the tectum to allow for separation of the axons to create mapping
 * Removed this content from lead section - it is completely uncited and far too much info for lead. Have left it here for anyone to go through and re-add to sections.--Iztwoz (talk) 09:34, 17 December 2017 (UTC)