Worm Breeder's Gazette 10(2): 121

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.

The unc-6 Gene is a Little Unstable in Institutional Settings

Edward Hedgecock, Joseph Culotti and David Hall

Figure 1

The products of three genes, unc-5,  
a reciprocal pair of adhesive gradients on the hypodermis that guide 
migratory cells and pioneer neurons dorsalward or ventralward, 
respectively (1987 CSH Meeting Abstracts, p. 73).  In particular, unc-
5 recessive mutations disrupt dorsalward migrations, unc 40 mutations 
primarily disrupt ventralward migrations, and unc-6 mutations disrupt 
migrations in either direction.  The unc-5 and unc-6 genes have been 
recently cloned and their partial sequences are described in this 
issue (Leung-Hagesteign et. al., Ishii et. al.).
If the unc-5,  interact it 
might be expected that some mutations in these genes could be 
phenotypically suppressed by compensatory mutations in other members.  
Moreover, if these genes do encode adhesive molecules, then extragenic 
suppressors of unc 5, unc-6, or unc-40 mutations might also identify 
genes which encode their receptors on migratory cells or growth cones. 
Finally, partial loss-of-function mutations, particularly in the 
pleiotropic unc-6 gene, might identify functional domains within the 
guidance molecules.  Here we describe several, apparently spontaneous, 
unc-6 mutations with unusual phenotypes and spontaneous unc-6 
revertants, including an extragenic suppressor which maps to the unc-5 
region of chromosome IV.
In an effort to understand the functional organization of the unc-5, 
e isolated new uncoordinated 
mutants following treatment with the bacterial frameshift mutagen ICR-
191.  As reported by other labs, this is not a potent mutagen in C.  
elegans; only 18 uncoordinated mutants were recovered from the progeny 
of approximately 100,000 treated Fl.  Conceivably, some or all of 
these 18 strains represent spontaneous rather than induced mutations.  
Surprisingly, 4 of the 18 strains carried unc 6 mutations.  The high 
proportion of unc-6 alleles in this small sample suggests that the unc-
6 gene is especially susceptible to ICR-191 or to spontaneous mutation.
We believe the latter as we recovered 13 additional uncoordinated 
mutants in a screen of the progeny of approximately 50,000 
unmutagenized F1.  One of these spontaneous strains carried an unc-6 
mutation (rh402).
The behavioral and cellular phenotypes of two of these possibly 
spontaneous unc-6 mutants, rh201 and rh203, are indistinguishable from 
ev400, a null EMS-induced allele of unc-6 (see Table).  Interestingly, 
the defects in the other three spontaneous unc-6 mutants, rh202, rh204,
and rh402, are largely confined to dorsalward migrations.  Thus these 
strains resemble e53, a null EMS-induced allele of unc-5.   A fourth 
mutant with defects largely confined to dorsalward migrations, unc-6 (
rh69) following EMS treatment.  Possibly all four of these dorsalward 
guidance defective alleles arose by a common, spontaneous mechanism 
rather than by chemical action.
Three strains carrying unc-6 null mutations have reverted during 
laboratory passage.  Two of these spontaneous revertants, unc-6 (rh46, 
ev436) and unc-6(ev400, ev437), represent intragenic events resulting 
in partial recovery of gene function.
Interestingly, the ev437 mutation preferentially restores dorsalward 
guidance, leaving a residual phenotype similar to that of unc-40 
recessive mutants.  The third revertant, unc-6(rh83), 
V), carries a semi-dominant mutation which 
can partially suppress unc-6(rh83), but not unc-6(ev400).  Preliminary 
mapping experiments have failed to separate sup (ev463) from unc-5.  
The frequent spontaneous loss or restoration of unc-6 gene function 
might be explained if this gene contains homologous domains which 
sometimes recombine unequally or convert one another.  These repeated 
domains might be specialized for different functions, e.g., guiding 
dorsalward or ventralward migrations.  It may be possible to separate 
sup (ev463) from unc-5 by genetic recombination or to prove its 
allelism to unc-5 by isolating new unc-5 mutations in the sup (ev463) 

Figure 1