Growth cone

A growth cone is a large actin-supported extension of a developing or regenerating neurite seeking its synaptic target.

[1] 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).

The sensory, motor, integrative, and adaptive functions of growing axons and dendrites are all contained within this specialized structure.

[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.

The filopodia are bound by a membrane which contains receptors, and cell adhesion molecules that are important for axon growth and guidance.

This region is composed primarily of a microtubule-based cytoskeleton, is generally thicker, and contains many organelles and vesicles of various sizes.

[4] 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.

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.

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.

The growth cones are continually being built up through construction of the actin microfilaments and extension of the plasma membrane via vesicle fusion.

Actin filaments are also constantly being transported away from the leading edge by a myosin-motor driven process known as retrograde F-actin flow.

Movement of the axons is controlled by an integration of its sensory and motor function (described above) which is established through second messengers such as calcium and cyclic nucleotides.

Growth cone receptors detect the presence of axon guidance molecules such as Netrin, Slit, Ephrins, and Semaphorins.

Image of a fluorescently-labeled growth cone extending from an axon F-actin (red) microtubules (green).
Two fluorescently-labeled growth cones. The growth cone (green) on the left is an example of a “filopodial” growth cone, while the one on the right is a “lamellipodial” growth cone. Typically, growth cones have both structures, but with varying sizes and numbers of each.
Model of growth cone-mediated axon guidance. From left to right, this model describes how the cytoskeleton responds and reorganizes to grow towards a positive stimulus (+) detected by receptors in the growth cone or away from a negative stimulus (-).