The bilaterally symmetric gustatory neuron pair ASEL/ASER displays directional asymmetric expression of several cell fate markers and senses and discriminates distinct inputs. The adult laterality of the ASE neurons is specified embryonically at the 4-cell stage and is dependent on the asymmetric lineage origins of ASEL and ASER (Poole and Hobert 2006). Despite their asymmetric origins, the ASE neurons are to a large extent molecularly and morphologically symmetric. Moreover, from the ABalppp/ABpraaa stage onwards the asymmetric lineages that give rise to ASE become bilaterally symmetric across the left-right axis and go on to produce identical pairs of neuronal and sheath cells on the left and right sides of the worm. How is bilateral symmetry re-imposed on these lineages and more specifically in the case of ASE what leads to the expression of the zinc finger transcription factor
che-1, the terminal selector of ASE cell fate, in two cells from asymmetric lineages? To address these issues we have performed a genome-wide RNAi screen for regulators of ASE cell fate (see abstract by Bashllari, Poole and Hobert). From this RNAi screen we have isolated
hlh-14/achaete-scute. We find in
hlh-14 mutants that ASE cell fate is completely lost, including the expression of
che-1. Intriguingly
hlh-14 expression is first observed at the ABalppp/ABpraaa stage, the stage at which the bilateral symmetry is re-imposed on these lineages. This expression persists to the comma stage in posterior lineage branches but is progressively lost from more anterior branches. Examination of other terminal cell fates within this lineage indicates that while the posteriorly situated ASE neurons are completely dependent on
hlh-14 anteriorly situated cells are not. Surprisingly, cells situated within the center of the lineage are partially dependent on
hlh-14. This suggests redundancy with a second gene in the center and anterior branches of the lineage. Cell lineage analysis indicates that when cells lose their fate in
hlh-14 mutants they are transformed to hypodermal cells. Taken together our data suggest
hlh-14 is required to establish neuronal cell fate in the posterior branches of the ABalppp/ABpraaa lineage as part of a mechanism that re-imposes bilateral symmetry on these lineages. We are currently investigating what regulates neuronal fate in the anterior branches of the lineage, how
hlh-14 expression is regulated and whether
hlh-14 plays additional roles in determining the terminal cell fate of the neurons in the posterior of the lineage.