To understand the molecular mechanisms of axon morphogenesis, we have been studying the
unc-115 gene.
unc-115 mutants display uncoordinated locomotion and defects in axon morphology. In wild type, the left fascicle of the ventral nerve cord (VNC) contains the axons of only four neurons, PVPR, PVQL, HSNL and AVKR. In
unc-115 mutants, the PVPR and PVQL axons extend in the right fascicle of the VNC instead of the left. The crossover of the HSNL and AVKR axons in
unc-115 mutants observed by Wightman and Garriga (pers. comm.) might result from defects in PVPR and PVQL axons, as PVPR and PVQL are pioneer axons for the left VNC (Garriga et al. 1993). The axons of phasmid neurons are also defective in
unc-115 animals (J. Zallen, pers. comm.). In wild type, the phasmid axons extend ventrally via the lumbar commisures, fasciculate at the ventral midline and extend anteriorly across the preanal ganglion as a single bundle. In
unc-115 mutants, the ventral extension is normal; however, in the anterior extension, the axons are defasciculated, are displaced dorsally and are shortened. Axons of other neurons might be defective, accounting for the uncoordination of
unc-115 animals. Possibly,
unc-115 mutation affects the ability of PVPR and PVQL axons to adhere to their substrate in the left VNC and the ability of the phasmid axons to adhere to each other and to their substrate in the preanal ganglion.
unc-115 encodes a polypeptide whose C-terminus is similar to the actin-binding headpiece domain of villin and whose N-terminus contains three LIM domains, motifs that mediate protein-protein interaction. We propose that UNC-115 affects axon morphology via interaction with the actin cytoskeleton of axons. A GFP fusion to sequences 2 kb upstream of
unc-115 through the entire
unc-115 coding region rescues the uncoordination of
unc-115 mutants. The fusion is expressed in all neurons, the pharynx and some hypodermal cells, and expression is first seen at the beginning of embryonic morphogenesis and persists to adulthood. In neurons, the UNC-115::GFP fusion protein is distributed uniformly in the processes and cell bodies and is excluded from the nucleus. In L1 larvae, UNC-115::GFP is present at the interfaces of the hypodermal seam cells and the main hypodermal syncytia. Additionally, UNC-115::GFP is seen in cell surface-associated oval-shaped plaques along the lengths of the excretory canals. These regions of UNC-115::GFP localization might be sites at which cell adhesion complexes, such as focal contacts, are linked to the actin cytoskeleton. UNC-115 might bind actin via its villin headpiece domain and recruit other factors, possibly cell adhesion components, to the actin cytoskeleton through interaction with its LIM domains. Furthermore, UNC-115 function might be modulated by guidance information present in the axon's substratum.