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Netrin is a class of protein involved in axon guidance, genetically conserved across C. elegans, Drosophila, frogs, and mice. The genes that encode the first discovered netrins was found to be 50% identical to the gene the unc-6 protein that plays a role in the development of neural systems in nematodes. It is named after the Sanskrit word "netr," which means "one who guides."
Netrin is a secreted molecule involved in both attractive and repulsive axon guidance, mediated through the UNC-40/DCC and UNC-5 receptors, respectively. Structurally, netrin resembles laminin. Mice deficient in netrin fail to form the hippocampal comissure or the corpus callosum.
The effect of netrins on growing axons is said to be chemotropic. A given axon may move toward a in the direction of higer netrin concentration (attractive effect), or may move away from higher concentrations (repulsive effect). Netrins also act as growth factors, encouraging cell growth activities in target cells.
The exact mechanism by which netrins guide neruon network development is still not fully known, as is the degree to which external factors determine neuronal networking, as opposed to internal factors programmed into the cells' genetic material.
A proposed model for netrin activity in the spinal column of developing human embryos is that netrins are released by a brain structure the floor plate. The netrins are picked up by receptor proteins embedded in the growth cones of targeted 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 and developing synapses with brain cells.
Once early pathways have been traced by axons, it is possible that newer axons follow the route set by older axons, rather than relying on guidance by netrins or related chemotropic factors.
The role of netrins in guiding axons in developing nervous systems was proposed by Dr. Mark Tessier-Lavinge and Dr. Tito Serafini—both of University of California San Fransisco—in 1994. They first identified the varieties of netrins dubbed "netrin-1" and "netrin-2."