Many sensory systems convey spatial information from the external world to the brain by forming an ordered set of neuronal connections known as a topographic map. We are studying the development of topographic maps formed by two sets of head sensory neurons in C. elegans, the IL1 and IL2 neurons. The IL2 neurons penetrate the worm's cuticle, and can be visualized in the living animal by incubation in the fluorescent dye DiO (C. Bargmann, pers. comm.) The IL1 neurons are visualized by an
unc-5::GFP expression construct (kindly provided by J. Culotti). Using these assays, we conducted genetic screens for mutations with defects in the IL1 and IL2 sensory maps. The screens resulted the isolation of several new alleles of
dig-1 (WBG 14(1):49), and a mutation in an unlinked gene with a phenotype similar to
dig-1. In
dig-1 animals, IL1 and IL2 sensory processes follow aberrant pathways to the nose; cell bodies are often misplaced as well. Temperature shift experiments using
dig-1 (
nu319ts) indicate that the temperature sensitive period for this phenotype is embryonic, suggesting that
dig-1 is required during the formation of the sensory map. In addition to sensory ending defects,
dig-1 animals exhibit several other phenotypes suggesting defects in adhesion, including a displaced gonad (Thomas et al., Cell 62:1041-52), and failure of adhesion between the cuticle in the buccal cavity and pharyngeal epithelial cells (WBG 12(3):105). Mapping data from Michael Basson and Jim Thomas indicated that
dig-1 maps very close to
sma-3 on the cluster of LGIII. The genome consortium has identified a very large gene (> 40 kb) in this region with homology to cell adhesion molecules of the Ig superfamily. Preliminary evidence indicates that two cosmids containing sequence of this gene show allele specific polymorphisms in two different
dig-1 alleles. In order to determine whether different functional domains of this gene could be involved in adhesion in different tissues, we are characterizing the relative severity of the adhesion defects of 7
dig-1 alleles in several tissues. We plan to physically map and sequence mutations in EMS-induced alleles. In
dig-1 animals, IL2 axons sometimes approach the nerve ring aberrantly, but then make a sharp turn just before reaching the ring, and enter the ring correctly. This phenotype may suggest that the axons detect a guidance cue at the ring that allows them to correct their trajectory. In the future, we plan to screen for genes involved in the expression and detection of such guidance cues by looking for mutations that enhance the phenotype of
dig-1 mutations.