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). Growth cones are situated on the tips of neurites, either dendrites or axons, of the nerve cell. The sensory, motor, integrative, and adaptive functions of growing axons and dendrites are all contained within this specialized structure.
Structure
The morphology of the growth cone can be easily described by using the hand as an analogy. The fine extensions of the growth cone are pointed filopodia known as microspikes. The filopodia are like the "fingers" of the growth cone; they contain bundles of actin filaments (F-actin) that give them shape and support. Filopodia are the dominant structures in growth cones, and they appear as narrow cylindrical extensions which can extend several micrometres beyond the edge of the growth cone. The filopodia are bound by a membrane which contains receptors, and cell adhesion molecules that are important for axon growth and guidance. In between filopodia—much like the webbing of the hands—are the lamellipodia. These are flat regions of dense actin meshwork instead of bundled F-actin as in filopodia. They often appear adjacent to the leading edge of the growth cone and are positioned between two filopodia, giving them a "veil-like" appearance. In growth cones, new filopodia usually emerge from these inter-filopodial veils. The growth cone is described in terms of three regions: the peripheral (P) domain, the transitional (T) domain, and the central (C) domain. The peripheral domain is the thin region surrounding the outer edge of the growth cone. It is composed primarily of an actin-based cytoskeleton, and contains the lamellipodia and filopodia which are highly dynamic. Microtubules, however, are known to transiently enter the peripheral region via a process called dynamic instability. The central domain is located in the center of the growth cone nearest to the axon. This region is composed primarily of a microtubule-based cytoskeleton, is generally thicker, and contains many organelles and vesicles of various sizes. The transitional domain is the region located in the thin band between the central and peripheral domains. Growth cones are molecularly specialized, with transcriptomes and proteomes that are distinct from those of their parent cell bodies. There are many cytoskeletal-associated proteins, which perform a variety of duties within the growth cone, such as anchoring actin and microtubules to each other, to the membrane, and to other cytoskeletal components. Some of these components include molecular motors that generate force within the growth cone and membrane-bound vesicles which are transported in and out of the growth cone via microtubules. Some examples of cytoskeletal-associated proteins are fascin and filamins (actin bundling), talin (actin anchoring), myosin (vesicle transport), and mDia (microtubule-actin linking).
Axon branching and outgrowth
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