We are interested in the question of how neurons choose synaptic partners. In
unc-4 mutants, VA motor neurons receive synaptic input normally reserved for their sister cells the VB motor neurons. As a result of the lost input to the VA's,
unc-4 mutants are unable to crawl backwards (1).
unc-4 encodes a homeodomain protein (2) that is expressed in VA but not VB motor neurons (WBG 12, #3,
p80 )which suggests that
unc-4 may regulate the expression of some feature of the VA's that allows presynaptic interneurons to distinguish them from their VB lineage siblings. We have previously described a selection strategy for isolating suppressors of the temperature sensitive allele
unc-4 (
e2322ts)(WBG 12, #3, pp 107-108) as a means of identifying the presumptive
unc-4 target gene. [
unc-4 (
e2322ts)contains a Leu to Phe substitution in the
unc-4 homeodomain.] Four dominant, extragenic suppressors and four dominant, intragenic revertants were isolated. All of these suppressors/revertants appear essentially wild type in an
unc-4 (ts)background which suggests that the normal pattern of input to VA motor neurons has been restored. The extragenic suppressors are within 0.07 map units to the left of
unc-87 suggesting that they are allelic. This interval includes the
unc-37 locus. Sydney Brenner isolated
unc-37 (
e262)and described it as a "coiler." We have noticed that
unc-37 (
e262)is also a phenocopy of
unc-4 (0)mutants; neither can crawl backwards and both coil dorsally (vulva on outside of loop) when touched on the head. This suggested that the
unc-4 suppressors are likely to be
unc-37 (gf)mutations. To test this idea, we screened for revertants of the suppressor
unc-37 (
wd17).EMS-mutagenized
dpy-5 (
e61)
unc-37 (
wd17 )I;
unc-4 (
e2322ts)IIhermaphrodites were mated at 25 C with
unc-4 (
e2322ts)males [grown at 16 C]. From ~10,000 F1 'swe obtained two revertants,
unc-37 (
wd17wd19)and
unc37 (
wd17 wd20 ).Both fail to complement
unc-37 (
e262).We propose therefore, that the
unc-4 suppressor mutations are in fact,
unc-37 (gf)alleles.
unc37 (
wd17 wd19 )and two other recently isolated
unc-37 alleles (3) are recessive lethals which suggests that
unc-37 (0)is lethal. Perhaps
unc-37 corresponds to an
unc-4 target gene encoding a cell surface receptor expressed in VA motor neurons and recognized by specific presynaptic interneurons. Alternatively,
unc-37 could encode a cofactor that interacts with the
unc-4 homeodomain. In either case, however,
unc-37 is also likely to provide essential functions in other cell types as well. We are now microinjecting cosmids to rescue
unc-37 (
e262).