The Influence of Pioneer Neurons on a Growing Motor Nerve inDrosophilaRequires the Neural Cell Adhesion Molecule Homolog FasciclinII

Abstract

The phenomenon of pioneer neurons has been known for almost a century, but so far we have little insights into mechanisms and molecules involved. Here, we study the formation of the Drosophila intersegmental motor nerve (ISN). We show that aCC/RP2 and U motor neurons grow together at the leading front of the ISN. Nevertheless, aCC/RP2 neurons are the pioneers, and U neurons are the followers, because only aCC/RP2 neurons effectively influence growth of the ISN. We also show that this influence depends on the neural cell adhesion molecule homolog FasciclinII. First, ablation of aCC/RP2 has a stronger impact on ISN growth than U ablation. Second, strong growth-influencing capabilities of aCC/RP2 are revealed with a stalling approach we used: when aCC/RP2 motor axons are stalled specifically, the entire ISN (including the U neurons) coarrests, demonstrating that aCC/RP2 neurons influence the behavior of U growth cones. In contrast, stalled U neurons do not have the same influence on other ISN motor neurons. The influence on ISN growth requires FasciclinII: targeted expression of FasciclinII in U neurons increases their influence on the ISN, whereas a FasciclinII loss-of-function background reduces ISN coarrest with stalled aCC/RP2 axons. The qualitative differences of both neuron groups are confirmed through our findings that aCC/RP2 growth cones are wider and more complex than those of U neurons. However, U growth cones adopt aCC/RP2-like wider shapes in a FasciclinII loss-of-function background. Therefore, FasciclinII is to a degree required and sufficient for pioneerfollower interactions, but its mode of action cannot be explained merely through an equally bidirectional adhesive interaction.

Specification ofDrosophilaaCC motoneuron identity by a genetic cascade involvingeven-skipped, grainandzfh1

“…Development 133 (8) number of genetic and cell-ablation studies have convincingly shown that aCC plays an instructive pioneer role and guides the follower U motoneurons along the ISN nerve Lin et al, 1995a;Sanchez-Soriano and Prokop, 2005). Our results lend support for the proposed instructive role of aCC in ISN formation.…”

A GATA/homeodomain transcriptional code regulates axon guidance through the Unc-5 receptor

“…It will be interesting to investigate the full array of guidance systems regulated by the eve-grn code. One potential candidate is FasII (Fas2 -FlyBase) (Landgraf et al, 1999) as it is an essential molecule for the pioneer function of aCC and RP2 (Sánchez-Soriano and Prokop, 2005).…”

Cell adhesion molecules in Drosophila synapse development and function

“…In aCC and RP2 pioneer axons, Fas II is necessary and sufficient for guiding follower axons and the establishment of presynaptic cell patterns [25]. At the NMJ, FasII is expressed at both presynaptic and postsynaptic site and is required for the accumulation of scaffolding protein Discs large (Dlg) and glutamate receptor subunits (GluRII A and GluRII B) [26].…”