Growth cone
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A growth cone is a large
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.[3] 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 "
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
Growth cones are molecularly specialized, with
(microtubule-actin linking).Axon branching and outgrowth
The highly dynamic nature of growth cones allows them to respond to the surrounding environment by rapidly changing direction and branching in response to various stimuli. There are three stages of axon outgrowth, which are termed: protrusion, engorgement, and consolidation. During protrusion, there is a rapid extension of filopodia and lamellar extensions along the leading edge of the growth cone. Engorgement follows when the filopodia move to the lateral edges of the growth cone, and microtubules invade further into the growth cone, bringing vesicles and organelles such as mitochondria and endoplasmic reticulum. Finally, consolidation occurs when the F-actin at the neck of the growth cone depolymerizes and the filopodia retract. The membrane then shrinks to form a cylindrical axon shaft around the bundle of microtubules. One form of axon branching also occurs via the same process, except that the growth cone “splits” during the engorgement phase. This results in the bifurcation of the main axon. An additional form of axon branching is termed collateral (or interstitial) branching;.[5][6] Collateral branching, unlike axon bifurcations, involves the formation of a new branch from the established axon shaft and is independent of the growth cone at the tip of the growing axon. In this mechanism, the axon initially generates a filopodium or lamellipodium which following invasion by axonal microtubules can then develop further into a branch extending perpendicular from the axon shaft. Established collateral branches, like the main axon, exhibit a growth cone and develop independently of the main axon tip.
Overall, axon elongation is the product of a process known as tip growth. In this process, new material is added at the growth cone while the remainder of the axonal cytoskeleton remains stationary. This occurs via two processes: cytoskeletal-based dynamics and mechanical tension. With cytoskeletal dynamics, microtubules polymerize into the growth cone and deliver vital components. Mechanical tension occurs when the membrane is stretched due to force generation by molecular motors in the growth cone and strong adhesions to the substrate along the axon. In general, rapidly growing growth cones are small and have a large degree of stretching, while slow moving or paused growth cones are very large and have a low degree of stretching.
The growth cones are continually being built up through construction of the actin microfilaments and extension of the
The growth capacity of the axons lies in the microtubules which are located just beyond the actin filaments. Microtubules can rapidly polymerize into and thus “probe” the actin-rich peripheral region of the growth cone. When this happens, the polymerizing ends of microtubules come into contact with F-actin adhesion sites, where microtubule tip-associated proteins act as "ligands". Laminins of the basal membrane interact with the integrins of the growth cone to promote the forward movement of the growth cone. Additionally, axon outgrowth is also supported by the stabilization of the proximal ends of microtubules, which provide the structural support for the axon.
Axon guidance
Movement of the axons is controlled by an integration of its sensory and motor function (described above) which is established through
A similar process is involved with
Growth cone receptors detect the presence of axon guidance molecules such as