Extracellular cues and pioneers act together to guide axons in the ventral cord of C. elegans.

The ventral cord is the major longitudinal axon tract in C. elegans containing essential components of the motor circuit. Previous studies have shown that axons grow out sequentially and that there is a single pioneer for the right axon tract which is important for the correct outgrowth of follower axons. Here, the dependencies between early and late outgrowing axons in the ventral cord were studied systematically with laser ablation experiments and a detailed analysis of mutants using multi-color GFP markers. Different classes of axon were affected to a different extent when the AVG pioneer neuron was eliminated. In the majority of the animals, axons were able to grow out normally even in the absence of the pioneer, suggesting that its presence is not absolutely essential for the correct outgrowth of follower axons. The transcription factor LIN-11 was found to be essential for the differentiation and pioneering function of the AVG neuron. UNC-30 appears to play a similar role for the PVP pioneer neurons. Later outgrowing axons typically do not simply follow earlier outgrowing ones, but subtle dependencies between certain groups of early and late outgrowing axons do exist. Different groups of axons growing in the same axon bundle apparently use different combinations of guidance cues for their navigation and can navigate largely independently.