Netrin

Netrins are a class of proteins involved in axon guidance. They are named after the Sanskrit word "netr", which means "one who guides." Netrins are genetically conserved across nematode worms, fruitflies, frogs, and mice. Structurally, netrin resembles laminin.

Netrins are chemotropic; a growing axon will either move towards or away from a higher concentration of netrin. Though the detailed mechanism of axon guidance is not fully understood, it is known that netrin attraction is mediated through UNC-40/DCC cell surface receptors and repulsion is mediated through UNC-5 receptors. Netrins also act as growth factors, encouraging cell growth activities in target cells. Mice deficient in netrin fail to form the hippocampal comissure or the corpus callosum.

A proposed model for netrin activity in the spinal column of developing human embryos is that netrins are released by the floor plate and are picked up by receptor proteins embedded in the growth cones of axons belonging to neurons in the developing spinal column. The bodies of these neurons remain stationary while the axons follow a path defined by netrins, eventually connecting to neurons inside the embryonic brain by developing synapses. It seems that once a pathway has been traced by an axon, new axons tend to follow it rather than being guided by netrins or related chemotropic factors.

Discovery
Netrin was first described in the nematode Caenorhabditis elegans in 1990, and named UNC-6, according to standard C. elegans naming protocol. The first mammalian homologue of UNC-6 was discovered in 1994, where it was discovered to be a vital guidance cue for rodent commissural axons in the spinal cord.

Netrin-1
Netrin-1 is a typical member of the netrin family displaying both attractive and repulsive cues depending on context. Retinal ganglion cell (RGC) axons convey visual information from the retina to the brain via the optic nerve head (ONH) and the optic nerve. During embryo development, RGC axon growth follows a path to the ONH assisted by the attraction of netrin-1 expressed by ONH cells. It is thought that the axon is then guided through the ONH to the optic nerve by repulsion induced by the presence of laminin at the ONH. Evidence for this reversal in response to netrin-1 is provided by the finding that Xenopus RGC axons are repelled by netrin-1 in the presence of laminin.