REGULATION OF INTERNEURON FUNCTION IN THE C-ELEGANS THERMOREGULATORY PATHWAY BY THE TTX-3 LIM HOMEOBOX GENE

Neural pathways, which couple temperature-sensing neurons to motor and autonomic outputs, allow animals to navigate away from and adjust met abolism rates in response to the temperature extremes often encountere d. ttx-3 is required for the specification of the AIY interneuron in t he C. elegans neural pathway that mediates thermoregulation. ttx-3 nul l mutant animals exhibit the same thermotactic behavioral defect as th at seen with laser ablation of AIY in wild type, suggesting that AIY d oes not signal in this mutant. ttx-3 encodes a LIM homeodomain protein . A ttx-3-GFP fusion gene is expressed specifically in the adult AIY i nterneuron pair, which connects to thermosensory neurons. In ttx-3 mut ant animals, the AIY interneuron is generated but exhibits patterns of abnormal axonal outgrowth. Thus, the TTX-3 LIM homeodomain protein is likely to regulate the expression of target genes required late in AI Y differentiation for the function of this interneuron in the thermore gulatory pathway. The ttx-3-dependent thermosensory pathway also coupl es to the temperature-modulated dauer neuroendocrine signaling pathway , showing that ttx-3 specifies AIY thermosensory information processin g of both motor and autonomic outputs.