Over half of the neurons in Caenorhabditis elegans send axon to the nerve r
ing, a large neuropil in the head of the animal. Genetic screens in animals
that express the green fluorescent protein in a subset of sensory neurons
identified eight new sax genes that affect the morphology of nerve ring axo
ns. sax-3/robo mutations disrupt axon guidance in the nerve ring, while sax
-5, sax-9 and unc-44 disrupt both axon guidance and axon extension. Axon ex
tension and guidance proceed normally in sax-1, sax-2, sax-6, sax-7 and sax
-8 mutants, but these animals exhibit later defects in the maintenance of n
erve ring structure. The functions of existing guidance genes in nerve ring
development were also examined, revealing that SAX-3/Robo acts in parallel
to the VAB-1/Eph receptor and the UNC-6/netrin, UNC-40/DCC guidance system
s for ventral guidance of axone in the amphid commissure, a major route of
axon entry into the nerve ring. In addition, SAX-3/Robo and the VAB-1/Eph r
eceptor both function to prevent aberrant axon crossing at the ventral midl
ine, Together, these genes define pathways required for axon growth, guidan
ce and maintenance during nervous system development.