Worm Breeder's Gazette 11(3): 40

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What Turns On mec-7?

Michel Hamelin and Joe Culotti

The 6 touch receptor neurons in C.  elegans are AVM, ALML ALMR, PVM, 
PLML and PLMR (Chalfie and Sulston, Dev.  Biol.  82:358).  Several 
genes are known to affect the generation, differentiation, and 
function of these cells.  Mutants of the gene mec-7 lack the large 
microtubules (15 protofilaments), a specific feature of the touch 
cells, and this results in touch insensitivity.  Since normal sized 
microtubules (11 protofilaments) are still produced in these cells, as 
well as in all other cells of mec-7 animals, the mec-7 , -tubulin is 
therefore specifically required for the generation of large 
microtubules.  A likely possibility is that mec-7 expression is 
confined to the touch cells.  In order to test this hypothesis, we 
brought a reporter gene under the control of the mec-7 promoter and 
generated transgenic animals.
Using Andy Fire's Ppd16.51 vector, we placed the lacZ coding region 
under the control of a 1.65 kb fragment that includes 0.85 kb upstream 
of the mec-7 start codon and 0.80 kb of the coding region.  This 
plasmid, named pNW115, was coinjected with pRF4, a marker plasmid 
carrying a dominant mutation of the rol-6 gene ( Mello et al., WBG 11(
1):18).  Transgenic rollers from the F1 were stained with X-Gal and 
expression of the mec-7-lacZ was found in all of the touch cells.  
Except for some occasional staining in a lateral pair of neurons just 
posterior to the pharynx (tentatively identified as FLP neurons), no 
other cells seem to express mec-7.  Since pNW115 lacks the SV40 
nuclear localization sequence, staining was sometimes observed along 
the axons, helping to confirm the identity of the neurons.
The roller and  -Gal staining phenotypes were found to be unstable 
in the subsequent generations (each roller yielding ~50% rollers), 
implying that the exogenous DNA is maintained as an extrachromosomal 
element.  This element, named evEX1, is likely to contain copies of 
both plasmids in a tandem array.  As a consequence of this instability,
each transgenic animal can be assumed to be a mosaic of cells 
containing evEX1 and of cells lacking it.  Indeed, in most animals, 
only a fraction of the touch cells are stained.  Among adult animals 
exhibiting at least one stained neuron, the percentages of stained 
cells of each type were: AVM: 30%; ALML or ALMR: 67%; simultaneous 
staining of both ALMs: 24%; PVM: 47% PLML or PLMR: 79%; simultaneous 
staining of both PLMs: 34%.  FLP neurons stained at a frequency of 3%. 
Expression was observed at all larval stages and in embryos too.
unc-86 lineage mutants lack several neurons including the six touch 
cells and the FLPs.  We genetically transferred evEX1 in unc-86 
animals and found no expression of mec-7.  When passed back into the 
wild type, this element re-expressed lac-Z in the touch neurons.
The mec-3 gene product, which is required for the maturation of the 
touch cells, is expressed only in these cells (with the exception of 
the FLPs and the PVDs) (Way and Chalfie, Genes & Dev.  3:1823), and is 
likely to be a transcription factor.  Therefore, an attractive 
assumption is that mec-3 directly activates the mec-7 gene.  We 
transferred evEX1 into mec-3 mutants and surprisingly, we found 
expression of mec-7 at almost normal levels in larvae, but at a lower 
level in adults.  Because of these results and because expression of 
mec-7 was not observed in PVD neurons, we conclude that mec-3 is not 
required to turn on mec-7, but is needed (directly or indirectly) for 
its maintenance in the touch cells.  With the goal of identifying the 
activator(s) of mec-7, we are currently studying its expression in 
other mutants affecting the generation and the maturation of the touch 
neurons.