Worm Breeder's Gazette 10(1): 85

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.

unc-104 Mutants Lack Directed Chemical Synapses

D.H. Hall and E. Hedgecock

The mutant unc-104 (rh43) is paralyzed, and grows slowly.  The 
epidermis is markedly reduced in volume along all four longitudinal 
cords.  Cell lineages and axon trajectories that have been examined 
appear normal.  The dorsal and ventral nerve cords are fully formed, 
the amphidial and phasmidial nerves appear normal, there is a nerve 
ring, and the PVP processes appear normal.  Some muscle arms from the 
dorsal body muscles extend medially to the dorsal nerve cord in fairly 
normal fashion, but others extend ventrally towards the ventral 
muscles and possibly to the ventral nerve cord.  Close examination of 
the dorsal and ventral nerve cords has revealed a complete absence of 
neuromuscular junctions (NMJs), despite the presence of motoneuron 
axons in the proper positions relative to the nerve/muscle plate.  A 
normal NMJ consists of a vesicle-filled swelling of the presynaptic 
motor axon with an electron dense structure attached to the inside of 
the presynaptic membrane directly apposed to the postsynaptic muscle 
arms.  In unc-104, the motor axons themselves seem deficient in 
synaptic vesicles along their length, although occasional clusters of 
vesicles are present.  No presynaptic densities are seen associated 
with these clusters in motor axons in either motor nerve.  The general 
lack of chemical synapses or NMJs within the nerve cords led us to 
examine the nerve ring in unc-104 in order to look for directed 
chemical synapses.  Processes in the nerve ring are also deficient in 
synaptic vesicles, and no presynaptic densities are found in 
association with the relatively few axon swellings which do contain 
vesicles.  It is possible that nondirected release of chemical 
transmitter(s) might still occur from these swellings, but the level 
of chemical synaptic transmission is presumably very low compared to 
wild type.  Electrical transmission between neurons is probably still 
effective, since gap junctions between neurons are still found.  The 
lack of presynaptic densities at neuron-neuron contacts within the 
nerve ring, as well as at neuron-muscle contacts along the motor 
nerves strongly suggests that unc-104 may be a gene product used to 
make these structures in the wild type.  Another possibility is that 
the gene product is required more generally in the process of cell-
cell recognition prior to forming a synapse.
Many neuron cell bodies in the vicinity of the nerve ring appear to 
be filled with synaptic vesicles, as are occasional neuron cell bodies 
in the ventral cord.  This is in contrast to the few vesicles within 
the axons, so one could argue that unc104 involves a defect in axonal 
transport.  Alternately, vesicle transport down the axon may be 
reduced in the absence of ongoing chemical transmission.  The 
relatively normal projections of neuronal axons and dendrites in unc-
104 also seems to argue against a defect in axonal transport.  The 
lack of neuromuscular input to dorsal body muscles is presumed to be 
responsible for their occasional misdirected muscle arms.  Similar 
misdirected muscle arms in dorsal body muscles were previously 
recognized as a secondary phenotype in many alleles of unc-5 and unc-6 
which lack motoneuron axons in the dorsal nerve cord (Hedgecock, 
Culotti and Hall, in preparation).  The viability of unc-104 is most 
encouraging; it may be feasible to do genetic studies in C.  elegans 
of many of the proteins required for synapse formation and synaptic 
transmission.  There are probably more genes which will produce a 
'synapseless' phenotype.  The paralyzed behavior and the presence of 
misdirected dorsal muscle arms should provide a simple means to screen 
for more mutants.