Worm Breeder's Gazette 10(3): 149

These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.

mec-6 Mutations Suppress Neuronal Degeneration

Marty Chalfie

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.