Pioneer axon is the classification given to axons that are the first to grow in a particular region. They originate from pioneer neurons, and have the main function of laying down the initial growing path that subsequent growing axons, dubbed follower axons, from other neurons will eventually follow.
Several theories relating to the structure and function of pioneer axons are currently being explored. The first theory is that pioneer axons are specialized structures, and that they play a crucial role in guiding follower axons. The second is that pioneer axons are no different from follower axons, and that they play no role in guiding follower axons.
Anatomically, there are no differences between pioneer and follower axons, although there are morphological differences. The mechanisms of pioneer axons and their role in axon guidance is currently being explored. In addition, many studies are being conducted in model organisms, such grasshoppers, zebrafish, and fruit flies to study the effects of manipulations of pioneer axons on neuronal development.
Santiago Ramon y Cajal, considered the father of modern neuroscience, was one of the first to physically observe growing axons. Moreover, he observed that axons grew in a structured, guided manner. He advocated that axons were guided by chemotactic cues. Indeed, later experiments showed that in both invertebrate and vertebrate models, axons grew along pre-determined routes to create a reproducible scaffold of nerves.
Ramon y Cajal's views faced some competition from those of Paul Alfred Weiss, his contemporary neuroscientist during the 1920s and 1930s. Weiss argued that functional specificity did not depend on specific axon connections, and that nonspecific mechanical cues participated in guiding axons. Subsequent investigations into chemotactics cues that started in the 1970s eventually proved that Ramon y Cajal's initial ideas were intuitive and ahead of his time.
The mechanism of growth of pioneer neurons has been investigated in the central and peripheral nervous systems of invertebrate animals.
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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, fruit flies, frogs, mice, and humans. Structurally, netrin resembles the extracellular matrix protein laminin. Netrins are chemotropic; a growing axon will either move towards or away from a higher concentration of netrin.
UNC-5 is a receptor for netrins including UNC-6. Netrins are a class of proteins involved in axon guidance. UNC-5 uses repulsion to direct axons while the other netrin receptor UNC-40 attracts axons to the source of netrin production. The term netrin was first used in a study done in 1990 in Caenorhabditis elegans and was called UNC-6. Studies performed on rodents in 1994 have determined that netrins are vital to guidance cues. The vertebrate orthologue of UNC-6, netrin-1 was determined to be a key guidance cue for axons moving toward the ventral midline in the rodent embryo spinal cord.
A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target. It is the growth cone that drives axon growth. Their existence was originally proposed by Spanish histologist Santiago Ramón y Cajal based upon stationary images he observed under the microscope. He first described the growth cone based on fixed cells as "a concentration of protoplasm of conical form, endowed with amoeboid movements" (Cajal, 1890).
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