Transcriptional control of neural function in C elegans

The C. elegans POU-homeobox gene unc-86 and LIM homeobox gene ttx-3 regulate the expression of downstream gene repertoires that mediate the complex recognition and signaling events necessary for neurogenesis and neural function. To identify the genetic cascades downstream of unc-86, we constructed a hyperactive UNC-86, by inserting the potent VPI6 transact!vation domain into an unc-86 genomic clone. UNC-86/VP16 can rescue an unc-86 null mutant. However this activated gene exhibits novel genetic activities that we have used to explore the genetic cascades downstream as well as transcriptional modulation in neural function. For example, UNC-86/VP16 dramatically enhances sensitivity to volatile odorants via expression in the major interneuron AIZ that is highly connected to the odorsensory neurons. UNC-86/VP16 may overexpress synaptic components in AIZ that connect to either presynaptic sensory neurons or postsynaptic motor neurons The strong hypersensitive phenotype is being suppressed to identify these unc-86 regulated genes. The LIM homeobox gene ttx-3 specifically affects thermotactic behavior and decouples metabolic control pathways from their usual temperature dependence. The neural pathway for thermotaxis includes the sensory neuron AFD and the connected interneurons AIY and AIZ. The ttx-3 null mutation exhibits the same behavioral defect as laser ablation of AIY and a ttx-3- GFP reporter gene is expressed specifically in the AIY interneuron pair. In ttx-3 mutants, AIY is generated but exhibits abnormal axonal projections. We hypothesize that ttx-3 regulates the connectivity of the AIY neuron so that in a ttx-3 mutant, AIY does not connect to one or many of its usual synaptic partners. We are using genetic analysis to identify these downstream genes.