Pioneer axon

Santiago Ramon y Cajal, considered the father of modern neuroscience, was one of the first to physically observe growing axons.

Indeed, later experiments showed that in both invertebrate and vertebrate models, axons grew along pre-determined routes to create a reproducible scaffold of nerves.

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.

[1] The mechanism of growth of pioneer neurons has been investigated in the central and peripheral nervous systems of invertebrate animals.

[1] Studies that involved selective destruction of guidepost cells resulted in pioneer axons becoming unable to navigate normally to the CNS from the PNS.

The route of extending growth cones has been shown to be abundant in glial cells, which are in turn part of a cellular mesh including other intermediate neurons and filopodia.

[3] A proposed mechanism involves the creation of a scaffold made out of interface glia, which growth cones contact during the establishment of axon tracts.

In addition, ablation of glia in later embryonic development also interfered with guidance of follower axons, showing that glial cells are necessary in maintaining scaffold needed for contacting growth cones.

Some of the various chemotactic cues that have been explored in the mechanisms of pioneer axons include netrin, ephrin, semaphorin, Slit-Robo, and Notch.

Ephrins primarily play a role in setting a gradient along the anterior-poster axis for the guidance of developing retinal axons.

In conjunction with the Robo receptor, Slit signaling played a role in determining tract positions parallel to the midline for longitudinal axons to follow during development.

The loss of either Slit or Robo caused dysfunction in the development of longitudinal pioneer neurons in the midbrain and hindbrain of Drosophila.

[6] Furthermore, it has been shown that Robo plays a diversified role in pioneer axon guidance in different areas of the brain during embryonic development.

The Notch receptor has been shown to interact with interface glia to form a path that longitudinal pioneer neurons can follow.

Remarkably, the majority of the tracts formed, indicating that other factors play a role in axon guidance that can correct for the loss of pioneer neurons.

The earliest differentiating pioneer neurons create a scaffold, with which growth cones of follower axons interact with.

[11] In a different study, replacement or removal of the early-born retinal ganglion cells, which function as pioneer neurons, had a significantly deleterious effect on the ability of later axons to exit the eye.

Subsequent axon-axon interactions were also shown to be necessary, as misrouting of retinal axons led to chiasm defasciculaiton, telencephalic and ventral hindbrain projections, or aberrant crossing in the posterior commissure.

Axonal pathfinding and fasciculation behaviour in the embryonic ventral nerve cord of Drosophila .