Homeodomain-containing proteins are a class of transcription factors that act at several levels of the cascade of developmental events that determine the final pattern of gene expression of each cell. Homeodomain proteins that determine the final differentiated features of neurons have been identified and studied in C. elegans (i.e. Lanjuin et al, 2003; Altun-Gultekin et al, 2001; Jin et al, 1994; Miller et al, 1992). At the meeting, we will describe our findings with
dsc-1, a gene that plays a similar role in determining the differentiation of enteric muscles.
dsc-1 was identified in a screen for suppressors of the slow defecation phenotypes of
clk-1 mutants (Branicky et al, 2001). In both the
clk-1 and wild-type backgrounds
dsc-1 mutants have a shortened defecation cycle. In addition,
dsc-1 mutants are defective in the last step of the defecation motor program, the expulsion step. However,
dsc-1 probably regulates the cycle length independently of the expulsion step, as overexpression of
dsc-1(+) can lengthen the cycle and other expulsion-defective mutants do not shorten the defecation cycle length of
clk-1 mutants. We have cloned
dsc-1 and found that it encodes a Q50 paired-like homeobox transcription factor that is expressed in a small subset of sensory neurons (AWA, AWC, ASE, FLP and PVD) and in a subset of enteric muscles, the two intestinal muscles (IM) and the anal depressor (AD), but not in the sphincter (S)). The anatomy of the enteric muscle is not affected by the absence of
dsc-1. Interestingly, the promoter of
dsc-1, isolated from internal sequences, directs expression to the sphincter, but not to the IM and AD. This suggests that
dsc-1 participates in a combinatorial code of expression that identifies as a group all muscles that are involved in defecation. We find that
dsc-1(+) is required in both the IM and the AD for a normal defecation cycle length and for the expulsion step of the motor program. We also find that
dsc-1(+) activity is required for the expression of
exp-1, a cation-selective GABA receptor that is required for the expulsion step, and that is expressed in the IM and the AD, as well as in the PDA neuron (Beg and Jorgensen, 2003). In the absence of
dsc-1, expression of
exp-1 is abolished in the IM and the AD but not in PDA. This strongly suggests that the expulsion defect of
dsc-1 mutants is due to loss of expression of
exp-1. We are currently determining if
dsc-1 affects the expression of other genes known to be expressed in the enteric muscles.