Book Description

Nervous system function, from sensory perception to motor control and cognition, requires the correct wiring of neural circuits during development. The establishment of these circuits consists of the growth and guidance of signal-sending axons and signal-receiving dendrites to their correct targets. Despite being exposed to the same molecular environment, a neuron's axon and dendrites have different morphologies and targets. Using the C. elegans DA9 motoneuron we explore mechanisms of dendrite growth and how a dendrite-specific response is achieved to a cue regulating axons and dendrites. We found that DA9 dendrite development is spatially and temporally distinct from the axon. While the axon grows embryonically, the dendrite develops postembryonically. Characterizing DA9 dendrite growth in larvae, adults and body size mutants suggests that it is not driven by size, but rather by a local cue. A candidate approach to identify this cue taught us that the guidance cue UNC-6/Netrin is required for both axon and dendrite development in DA9. The UNC-6 repulsive receptor UNC-5 repels the axon from the ventral nerve cord, while the attractive receptor UNC-40 is dendritically enriched and promotes antero-posterior dendrite growth. While ventrally secreted UNC-6 instructs axon guidance, dorsal or even membrane-tethered UNC-6 can support dendrite development. Surprisingly, the kinase PAR-4/LKB1 is selectively required for UNC-40 signaling in dendrite outgrowth. Finally, we found that the C-terminal motor kinesin KLP-16 also promotes DA9 dendrite growth and that its enrichment at the DA9 dendrite distal tip may be partially regulated by PAR-4/LKB1. These data suggest that axon and dendrite of one neuron interpret common environmental cues with different receptors and downstream signaling pathways.