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. Netrin-1 has been identified as a critical component of embryonic development with functions in axon guidance, cell migration, morphogenesis and angiogenesis. The most recent studies have found that there are 5 types of netrins expressed in animals. Ectotopic expression of UNC-5 can result in short or long range repulsion.
The guidance of axons to their targets in the developing nervous system is believed to involve diffusible chemotropic factors secreted by target cells. Floor plate cells at the ventral midline of the spinal cord secrete a diffusible factor or factors that promotes the outgrowth of spinal commissural axons and attracts these axons in vitro. Recent studies indicate that several axon guidance mechanisms are highly conserved in all animals, whereas others, though still conserved in a general sense, show strong evolutionary divergence at a detailed mechanistic level. Expression of UNC-6 netrin and its receptor UNC-5 is required for guiding pioneering axons and migrating cells in C. elegans. Netrins are axon guidance molecules that transmit their activity through 2 different receptors. The function of UNC-5 is to repel axons while the other receptor UNC-40 (or Deleted in Colorectal Cancer) attracts axons to the source of UNC-6 production. Methods such as antibody staining, transgene expression and microarray analysis have confirmed that UNC-5 is expressed in DA9 motor neurons.
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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.
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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