Expression of the unc-4 homeoprotein in Caenorhabditis elegans motor neurons specifies presynaptic input

In the nematode, Caenorhabditis elegans, VA and VB motor neurons arise from a common precursor cell but adopt different morphologies and synapse with separate sets of interneurons in the ventral nerve cord. A mutation that inactivates the unc-4 homeodomain gene causes VA motor neurons to assume the VB pattern of synaptic input while retaining normal axonal polarity and output; the disconnection of VA motor neurons from their usual presynaptic partners blocks backward locomotion. We show that expression of a functional unc-4-beta-galactosidase chimeric protein in VA motor neurons restores wild-type movement to an unc-4 mutant. We propose that unc-4 controls a differentiated characteristic of the VA motor neurons that distinguishes them from their VB sisters, thus dictating recognition by the appropriate interneurons. Our results show that synaptic choice can be controlled at the level of transcription in the post-synaptic neuron and identify a homeoprotein that defines a subset of cell-specific traits required for this choice.