The UNC-4 homeoprotein is expressed in specific cholinergic motor neurons (VA, DA, VC, SAB). In
unc-4 mutants, VA motor neurons receive synaptic input from interneurons normally reserved for their VB sister cells. Therefore, UNC-4 is required for the creation of proper synaptic inputs to VA motor neurons. UNC-4 is also required for maintaining normal levels of synaptic vesicle proteins. In
unc-4 mutants, Choline acetyltransferase (ChAT), vesicle acetylcholine transporter (UNC-17), and synaptotagmin (SNT-1) are substantially reduced in in all
unc-4 expressing neurons (K. Lickteig et al., this meeting) (1). These data indicate that UNC-4 may control differentiation of motor neuron synaptic output in addition to specifying VA motor neuron synaptic input. In an effort to identify other genes which functionally interact with
unc-4 in these developmental processes, we have conducted screens for
unc-4 modifier mutations. Here we report the isolation of new alleles of
egl-19 that either suppress or enhance the Unc-4 backward movement defect. The semidominant mutation,
wd29, weakly suppresses specific
unc-4 alleles.
wd29 fails to suppress
unc-4 nulls and deletions but does compensate for certain missense mutations in the UNC-4 homeodomain and Engrailed-like domain (A. Winnier et al., this meeting) (2). Genetic mapping versus morphological markers and Tc1 polymorphisms placed
wd29 in a 0.3 map unit interval between the physical markers
stp44 and
unc-24 on chromosome IV. Deletions that cover this interval fail to enhance the Unc-4 suppressor activity of
wd29 which is likely to mean that
wd29 represents a rare gain-of-function mutation. This interpretation is consistent with the subsequent isolation of a recessive revertant allele,
wd29wd45, which also maps to the
stp44-
unc-24 interval. Homozygous
wd29wd45 enhances the
unc-4 temperature sensitive allele,
e2322ts, at permissive temperature but does not produce an Unc-4 like backward movement defect in an
unc-4(+) background.
wd29wd45 animals display the slightly long and mildly egg-laying defective phenotype of certain
egl-19 loss-of-function alleles.
wd29wd45 fails to complement these Egl-19 traits in the hypomorphic alleles
n582,
ad1015, and
ad1006. Thus, we conclude that
wd29 and
wd29wd45 are likely to represent new
egl-19 alleles. EGL-19, an L-type calcium channel, is widely expressed in the nervous system and in muscle cells. Although
egl-19 is required for normal muscle function, a role for
egl-19 in neurons has not been defined (3). Our results may indicate that
egl-19 function is also important for motor neuron synaptic activity. 1. Lickteig, K. et al., 1997 International C. elegans Meeting. 2. Winnier, A. et al., 1997 International C. elegans Meeting. 3. Lee, R. et al. (1997) EMBO J. 16: 6066-6076.