Pioneer Axon - Role of Pioneer Axons in Neuronal Development

Role of Pioneer Axons in Neuronal Development

The role of pioneer axons in neuronal development has been studied extensively in various invertebrate and vertebrate systems in both the central nervous system and peripheral nervous system. Although these experiments have shed light on the functions of the pioneer axons, the results reveal conflicting information into the extent of the effect of pioneer axons on proper development. In addition, other studies have shown that certain cells that interact with pioneer axons are also crucial in the eventual development of neural pathways, and that loss of these cells results in improper navigation of pioneer axons. Furthermore, identical pathways and homologous neurons across different species reflect different pathfinding abilities of growth cones in pioneer neurons.

An investigation was conducted looking into the role of pioneer axons in the formation of both CNS and PNS axon pathways in a Drosophila embryo. Using a method to ablate specific neurons, the ablation of the aCC axon, which plays a role in pioneering the intersegmental nerve in the Drosophila PNS, resulted in the three typical follower axons becoming delayed and prone to pathfinding errors. Despite these consequences, eventually the pathway was formed in the majority of subjects. Ablation of the pioneer axons that formed the longitudinal tracts in the Drosophila CNS resulted in similar difficulties in the formation and organization of longitudinal pathways in 70% of observed segments. Ultimately, like in the PNS, the longitudinal pathways formed in about 80% of observed segments. Thus, it was shown that the pioneer axons played a role in the development of the CNS and PNS, and without the pioneer axons, the growth of the followers was delayed. 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.

Although studies of the mechanisms of pioneer axons have mostly been in invertebrate models, studies have also begun exploring the role of pioneer axons in the development of large vertebrate axon tracts. The primary model for these experiments has been in the zebrafish. Like in Drosophila, there is evidence to show that although pioneer axons play an important role in guiding the growth cones of follower axons, they may not be completely essential. The brain of the early zebrafish presents an ideal environment in which to study the behavior of developing axon tracts. The earliest differentiating pioneer neurons create a scaffold, with which growth cones of follower axons interact with.

Deletion of pioneer axons which create the scaffold have an effect on the growth cones of the neurons of the nucleus of the posterior commissure, in that they cannot follow the normal path of extending ventrally, then posteriorly. Despite the compromised pioneer neuron scaffold, the follower growth cones extend ventrally normally. However, around half of the followers do not follow the posterior longitudinal path correctly, while the other half do. This suggests that other cues other than those from pioneer axons play a role in guiding follower axon growth, and that pioneer axons may play different roles in different parts of neuronal development. 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.