Three mutations in
mec-4 (
e1661,
u214, and
u231) and a single mutation
deg-1(
u38) result in the degeneration of different sets of neurons. The
mec-4 mutations cause the death of the touch cells, and the
deg-1 mutation causes the death a number of cells including the IL1 sensory cells and the PVC and AVD interneurons. These mutations are dominant; recessive mutations of these genes do not result in cell death. I have made a number of double mec mutants with the
mec-4d to determine whether defects in any other touch gene can affect the touch cell degenerations. John Sulston and I showed in the initial description of the touch mutants (Dev. Biol. 82: 358, 1981) that unc- 86 and
mec-3 mutations will prevent the
mec-4d deaths. This result demonstrates the specificity of the action of the
mec-4 gene, since touch cells are not made in these mutant backgrounds. Mutations in two other touch genes prevent the
mec-4d deaths.
lin-32 mutations affect the lineages that give rise to the touch cells, so it is not surprising fewer dying cells are seen in the mutants. It was surprising, however, to find that mutations in
mec-6 do prevent the
mec-4d degenerations. Although all double mutant combinations have not been made, thirteen different
mec-6; ave been made using seven of the nine existing
mec-6 mutations and all three of the
mec-4d mutations. In all cases the
mec-6 mutations prevented the touch cell death (because the animals are touch insensitive, the presence of the touch cells was confirmed in young adults by Nomarski observations). One of the
mec-6 mutations (
u247) is temperature sensitive, and its affect on the degenerations produced by all three
mec-4d mutations was also temperature dependent. The cells die at 15 C. Shifting the mutants to 15 C at hatching, however, did not result in the subsequent death of the cells. Either the mec- 4d mutations cannot cause the later death of the touch cells or the suppression caused by the
mec-6 mutant product was already irreversible by hatching. The
mec-6 mutations (three have been used) also suppress the neuronal deaths caused by the
deg-1 mutation.
deg-1 mutants do not move when prodded on the tail with a worm pick, but
mec-6 and
mec-6; do respond when hit with the pick (these animals are still insensitive to the gentler touch of an eyebrow hair). No degenerations are seen in the double mutants (this includes the IL1 cells and other neurons near the nerve ring that usually die in the early L1). Thus, the
mec-6 suppression does not exclusively effect cells of the touch circuit. These results indicate that even though the only detectable defect of
mec-6 mutants is touch insensitivity, the gene is required for the function of a number of types of nerve cells.
mec-6 mutations, thus, suppress the deaths of different sets of nerve cells caused by mutations in two different genes. This finding indicates that there is an underlying molecular similarity in the deaths caused by the
mec-4 and
deg-1 mutations.
mec-6 mutations identify one component that is needed for the degenerative process. The role of
mec-6 in this process is not clear. If the
mec-4 and deg- 1 mutant products directly cause the degeneration, the
mec-6(+) product may be needed to produce functional products from mutant (and, perhaps, wild-type) genes. Alternatively,
mec-6 could cause the degenerations, but only when appropriately altered by the action of the
mec-4d and
deg-1 mutant products. In any case,
mec-6 has turned out to be a rather intriguing gene.