Genetic mechanisms for axonal development of ray sensory neurons and behavior in the Caenorhabditis elegans male

Abstract

Understanding the assembly of sex-specific circuits will help to elucidate the neural networks underlying complicated mating behaviors. In this study, I tried to understand the genetic mechanisms of axon guidance of ray sensory neurons in the C. elegans male, which are required for copulation. I investigated how the known guidance genes and potentially new genes affect the establishment of these circuits. One major conclusion through this study is that ray axon pathfinding relies on a combination of general guidance cues and ray-specific genes. Ray commissures may either pioneer their routes or follow the preexisting tail commissures during postembryonic development. The global guidance cue UNC-6/netrin-UNC-40/DCC provides the primary dorsoventral guidance cue to ray axons for dorsoventral migration. Anterior axon growth cones also respond to an unknown antero-posterior cue(s). Among 6 potentially new rax genes, rax-1 and rax-4 are highly specific to ray neurons and appear to be required for dorsoventral migration; rax-2 and rax-3 affect the antero-posterior signaling for both ray neuron cell bodies and their axons or for the cell fate determination. rax-5 and rax-6 affect both axon guidance and ray morphology. Further characterizing their molecular identities should provide a basis for understanding the mechanisms underlying ray commissure development. In addition, the maintenance of processes of ray neurons requires the SAX-1/NDR and SAX-2/FRY signal pathway as other sensory neurons.;Another gene egl-35 was studied in detail. egl-35(bx129) adult males lack both mate-searching and copulatory behaviors, which are similar to larval males, suggesting that egl-35(bx129) males have an immature nervous system. egl-35 mutants display several malformations of the nervous system: abnormal axon guidance of ray neurons, mis-regulated expression of serotonin in CP motorneurons and failure to migration of two putative neuroendocrine XXX cells. egl-35 can interact with the heterochronic genes let-7 and lin-14 to regulate the timing of larval development. These observations raise the possibility that egl-35 switches the timing of maturation of neurons underlying adult sexual behaviors. I found that egl-35 encodes a SWI/SNF like ATPase, a component of Tip60/NuA4-like HAT complex, suggesting EGL-35 could regulate the expression of genes required for neuron maturation.