We are interested in the development and function of the GABAergic D neurons in the ventral cord. These neurons mediate the coordinated sinusoidal motion of the worm by inhibiting body wall muscle contractions. D neurons in
unc-30 mutants do not produce GABA, are defective in axonal pathfinding, and fail to make proper synaptic connections(J.White, personal communication).
unc-30 encodes a homeodomain transcription factor expressed in all D neurons (Jin Y, Hoskins R and Horvitz HR Nature 372: 780), suggesting that UNC-30 controls transcription of genes that are involved in D neuron differentiation and function.
unc-47 mutant worms express higher levels of GABA than wild type animals and display a similar locomotion phenotype to that of
unc-30 (McIntire SL, Jorgensen E and Horvitz HR Nature 364:334).
unc-47 has been shown to encode the vesicular pump for GABA and is expressed in all GABAergic neurons (K. Schuske and E. Jorgensen, WCWM 1996). The phenotype of
unc-47 worms and the expression pattern of
unc-47 suggest that it might be regulated by
unc-30. We crossed the
unc-47-GFP array (gift of Kim Schuske and Erik Jorgensen) into an
unc-30 null mutant. In the
unc-30 mutant background,
unc-47 expression was abolished in the D neurons whereas its expression in other GABAergic neurons was unaffected, suggesting that
unc-30 regulates transcription of
unc-47 in the D neurons. Experiments to identify the
unc-47 promoter elements regulated by
unc-30 are underway. We will present this analysis at the meeting.