Mutations affecting dauer larva formation result in one of two phenotypes: dauer defective (Daf-d) or dauer constitutive (Daf-c). Daf-d mutants do not form dauers under dauer-inducing conditions, whereas Daf-c mutants form dauers under non-inducing conditions. Ciliated sensory neurons in the amphids mediate the response to these environmental conditions. Mutations that affect the morphology of these ciliated sensory endings are usually Daf-d.
daf-19 mutants are the exception: they completely lack ciliated endings and are Daf-c. All three alleles of
daf-19 (
m86,
sa190,
sa232) are strongly Daf-c: ca. 70% or more dauer larvae at 15 C, ca. 95% or more at 25 C (dauer formation is an inherently temperature sensitive process). The unusual combination of phenotypes could be due to a cell fate specification defect during amphid neuron development. Killing the amphid neurons ADF, ASI and ASG causes a Daf-c phenotype, suggesting that impaired development of amphid neurons can trigger dauer formation. By analysis of daf-d;
daf-19 double mutants, we have positioned
daf-19 in the formal genetic pathway for dauer formation.
daf-19 is epistatic to Daf-d mutations in both parallel branches of this pathway and lies upstream of the Daf-d gene
daf-12. The genes in the parallel branches are thought to be important for sensory response leading to dauer formation, whereas the genes downsteam and including
daf-12 are thought to be important for the reception of amphid neuronal signals by target tissues and for the activation of dauer larva morphogenesis. A possible interpretation of epistasis analyses is that
daf-19 affects a basic function of the amphid neurons involved leading to a Daf-c sensory response. Germline transformation rescue experiments demonstrated that two overlapping cosmid clones, ZK945 and F27E5, individually rescue
daf-19 phenotypes. Subsequent rescue by various subclones from the 9 kbp overlap region revealed that
daf-19 is the same as the gene F27E5.5 (predicted by the C. elegans genome project). Database searches and comparisons showed that this gene encodes a novel protein with several putative transmembrane domains and weak similarity to human melanocortin peptide hormone receptors. Melanocortins have diverse functions, including regulating nerve cell growth during development and regeneration after damage. Taken together the results suggest that
daf-19 might encode a protein involved in cell specification or morphogenesis of amphid sensory neurons. Mutations in
daf-19 may thus interfere with the normal dauer formation signalling by causing misspecification of neurons.