VA and VB motor neurons arise as sister cells, but adopt different synaptic inputs and axonal trajectories. Ventral contractions during backward movement depend on synaptic input to VA motor neurons from one set of interneurons (AVA, AVD, AVE) whereas ventral contractions during forward movement depend on input to the VBs from a separate set of interneurons (AVB, PVC). In
unc-4 mutants, VA motor neurons adopt a pattern of synaptic input normally reserved for their VB sister cells. One explanation for this effect is that the UNC-4 homeoprotein functions in the VAs to prevent expression of genes that specify VB-type inputs. This model is consistent with the finding that
unc-4 activity depends on UNC-37, a homolog of Groucho which functions as a transcriptional corepressor protein in flies. In addition, the VB-specific reporter genes,
acr-5::gfp and
del-1::gfp, are ectopically expressed in VA motor neurons in
unc-4 and
unc-37 loss-of-function mutants (1). If UNC-4 and UNC-37 function in the VAs to negatively regulate genes which specify VB synaptic inputs, our model predicts that ectopic expression of UNC-4 in the VB motor neurons should disconnect the VBs from the forward movement circuit. To test this prediction, we have expressed UNC-4 in the VBs using the
del-1 promoter. An integrated
del-1::
unc-4 array (wdIs2) produces a distinctive forward movement defect that is consistent with the loss of normal inputs to the VBs. This effect is correlated with VB-specific repression of
acr-5::gfp in wdIs2 animals. As presumptive membrane proteins, ACR-5 (nicotinic acetylcholine receptor alpha subunit) and DEL-1 (degenerin-like sodium channel) could act at the cell-surface to specify VB-type synaptic inputs. A major goal of this work is to determine the effects of
del-1 and
acr-5 mutations on VB differentiation. wdIs2 animals also display strong ventral coiling during backward movement. One explanation for this phenotype is that UNC-4 is sufficient to miswire the VBs with VA-type synaptic inputs, thus adding the VBs to the backward movement circuit. This result may mean that UNC-4 is required for expression of VA specifying genes in addition to its requirement for repression of VB-specifying genes. EM reconstruction is currently in progress to reveal whether the wdIs2 uncoordinated phenotype can be attributed to miswiring of the VBs with VA type inputs. 1. Ross, J., et al. 1997 C. elegans Meeting