Our lab is interested in the regulation of neurotransmitter biosynthesis under aversive conditions. Using GFP reporters, we found that the expression of GABA synthesis gene
unc-25/glutamic acid decarboxylase was increased, while acetylcholine (ACh) synthesis gene
cha-1/choline acetyltransferase was reduced in dauer animals. By contrast, we observed that in starved L1 animals, the expression of both
unc-25::gfp and
cha-1::gfp was decreased, suggesting that GABA biosynthesis is differentially regulated under distinct aversive conditions. A previous report indicated that the RFX transcription factor DAF-19 is expressed in the locomotory neurons and
daf-19 mutants exhibited enhanced resistance to aldicarb (Senti and Swoboda, 2008). We found that
daf-19::gfp levels in the locomotory neurons was reduced in wild-type dauers. Since either reduced ACh neurotransmission or increased GABA neurotransmission could lead to enhanced resistance to aldicarb (Loria et al., 2004; Vashlishan et al., 2008), we analyzed
unc-25::gfp and
cha-1::gfp in
daf-19 mutants. We observed that
cha-1::gfp was reduced in
daf-19 mutants. Furthermore, we found that the expression of
unc-25 and
unc-47/vesicular GABA transporter was significantly increased in both
daf-19(
m86) and
daf-19(
yz70) mutants. While several previous studies have shown that DAF-19 acts as a transcriptional activator (Swoboda et al., 2000; Wang et al., 2010; Xie et al., 2013), our results suggest that DAF-19 may also act as a negative regulator of GABA neurotransmission under optimal growth conditions. Enhanced GABA neurotransmission could represent a genetic program that inhibit un-necessary locomotion under aversive growth conditions and may contribute to the characteristic relax appearance of dauers. References: Loria PM, Hodgkin J and Hobert O, 2004. J. Neurosci. 24:2191-2201.Senti G and Swoboda P, 2008. Mol Biol Cell 19(12):5517-28.Swoboda P, Haskell T, Adler HT and Thomas JH, 2000. Mol Cell 5:411-421.Vashlishan AB, Madison JM, Dybbs M, Bai J, Sieburth D, Ch'ng Q, Tavazoie M and Kaplan JM, 2008. Neuron 58:346-361.Wang J, Schwartz HT, Barr MM, 2010. Genetics 186:1295-1307.Xie Y, Moussaif M, Choi S, Xu L and Sze JY, 2013. PLoS Genet 9(3):
e1003324.