Innexins are transmembrane proteins, and form gap junction channels and non-junctional hemichannel. Innexins are known to play fundamental roles in the information processing in the nervous system. We previously showed that INX-4, a member of innexin family, is required for thermotaxis and functions in the AFD thermosensory neuron. Since the thermotaxis abnormality of
inx-4 mutants was very mild, we hypothesized that other innexins might also function to regulate thermotaxis. To test this hypothesis, we examined the thermotaxis behaviors of most of the innexin gene mutants present in the C. elegans genome and also assessed whether overexpression of the innexin genes in AFD affects thermotaxis. Our genome-wide survey revealed that UNC-7/Innexin is important for regulation of thermotaxis; overexpression of UNC-7 in AFD caused a thermophilic defect. We also generated strains lacking
unc-7 only in AFD using Cre/loxP system and found that
unc-7(AFD KO) animals displayed a cryophilic defect. These results indicate that UNC-7 functions in AFD to regulate thermotaxis. To identify the critical period of
unc-7, we utilized the auxin-inducible degron system and found that the activity of
unc-7 in AFD is required later than the larval stage, suggesting that
unc-7 acts at the stage after the development of AFD is completed. Calcium imaging revealed that
unc-7 mutations did not affect temperature-evoked calcium response in AFD, indicating that UNC-7 functions in the downstream of calcium influx. We also investigated whether UNC-7 functioned as gap junctions or hemichannels. Previous study indicated that the UNC-7(Cysless), in which four cysteines in the extracellular loops are substituted to alanine, cannot form gap junction while maintaining the hemichannel activity. We therefore asked whether UNC-7(Cysless) can rescue the thermotaxis defect of
unc-7(AFD KO) animals. While the expression of wild-type UNC-7 only in AFD rescued thermotaxis defect of
unc-7(AFD KO) animals, UNC-7(Cysless) did not. This result suggests that UNC-7 regulates thermotaxis by functioning as gap junctions. Our results suggest that UNC-7 functions as gap junctions to transmit temperature information from AFD to another neuron. We are currently identifying the gap junction partner innexin and neuron of UNC-7 in AFD. Through our research, we hope to understand the role of UNC-7-mediated gap junction in thermotaxis and reveal the dynamics of the gating of gap junctions during animal behavior.