Regulatory programs that control the specification of serotonergic neurons have been investigated by genetic mutant screens in the nematode Caenorhabditis elegans. Loss of a previously uncloned gene,
ham-3, affects migration and serotonin antibody staining of the hermaphrodite-specific neuron (HSN) pair. We characterize these defects here in more detail, showing that the defects in serotonin antibody staining are paralleled by a loss of the transcription of all genes involved in serotonin synthesis and transport. This loss is specific to the HSN class as other serotonergic neurons appear to differentiate normally in
ham-3 null mutants. Besides failing to migrate appropriately, the HSNs also display axon pathfinding defects in
ham-3 mutants. However, the HSNs are still generated and express a subset of their terminal differentiation features in
ham-3 null mutants, demonstrating that
ham-3 is a specific regulator of select features of the HSNs. We show that
ham-3 codes for the C. elegans ortholog of human BAF60, Drosophila Bap60, and yeast Swp73/Rsc6, which are subunits of the yeast SWI/SNF and vertebrate BAF chromatin remodeling complex. We show that the effect of
ham-3 on serotonergic fate can be explained by
ham-3 regulating the expression of the Spalt/SALL-type Zn finger transcription factor
sem-4, a previously identified regulator of serotonin expression in HSNs and of the
ham-2 Zn transcription factor, a previously identified regulator of HSN migration and axon outgrowth. Our findings provide the first evidence for the involvement of the BAF complex in the acquisition of terminal neuronal identity and constitute genetic proof by germline knockout that a BAF complex component can have cell-type-specific roles during development.