Molecular Biological Analysis of Behavioral Control in the Nematode C. elegans

通过对食物、饥饿和气味刺激在线虫学习行为和其他功能中的作用的遗传和分子生物学研究，我们获得了以下结果。优雅(1)学习丁酮和食物。我们发现，预先暴露于丁酮和食物，特别是增强了对丁酮的趋化性，并分析了这种行为的突变体。这种行为需要位于AWC-ON神经元感觉纤毛上的Bardet-Biedl综合征基因的功能，AWC-ON神经元感觉丁酮。它还需要G α蛋白ODR-3中的特定氨基酸残基，该氨基酸残基与气味受体偶联，这表明可能涉及与G α相互作用的蛋白质。(2)控制肠道内的生长速度等。我们对控制肠内生长速率等的1类flr基因进行了基因内分析。2类flr基因与1类flr基因相互作用，也调节对大肠杆菌的免疫。杆菌这些基因之一，flr-2，编码在神经元中表达的DAN/Gremlin/Cerberus家族的分泌蛋白。我们确定了FLR-2结合蛋白ZK20.1，调节排便周期。(3)dauer幼虫规律分析。我们研究了大量的数据，已知突变的合成dauer组成的表型，他们的抑制另一个突变，和表达的dauer信号传导分子p2p-7在各种突变背景。(4)预先暴露于令人厌恶的气味剂的行为变化。预暴露于壬酮增强了对壬酮的回避。这种可塑性与暴露前食物的存在无关，并且需要多巴胺，多巴胺在人类行为可塑性中起着重要作用。(5)平行路径的遗传学理论。从上位性数据推导出信号通路中基因顺序的遗传理论被扩展到平行通路的情况。新理论成功地解释了某种神秘现象。

We obtained the following results in genetic and molecular biological studies on the roles of food, starvation, and repellent odorants in learning behaviors and other functions of the nematode C. elegans. (1) Learning with butanone and food. We discovered that pre-exposure to butanone and food specifically enhances chemotaxis to butanone, and analyzed mutants in this behavior. The behavior required the functions of Bardet-Biedl syndrome genes at the sensory cilia of the AWC-ON neuron, which sense butanone. It also required a specific amino acid residue in the G alpha protein ODR-3, which couples with odorant receptors, suggesting that a protein interacting with G alpha may be involved. (2) Control of growth rates etc. in the intestine. We conducted intragenic analysis of class 1 flr genes, which control growth rates, etc. in the intestine. Class 2 flr genes, which counteract the class 1 genes, also regulated immunity against E. coli. One of these genes, flr-2, encoded a secretory protein of the DAN/Gremlin/Cerberus family that was expressed in neurons. We identified a FLR-2-binding protein ZK20.1, which regulated defecation cycle periods. (3) Analysis of dauer larva regulation. We examined a large amount of data on the synthetic dauer-constitutive phenotypes of known mutations, their suppression by another mutation, and the expression of the dauer-signaling molecule DAF-7 in various mutant backgrounds. (4) Behavioral changes by pre-exposure to repellent odorants. Pre-exposure to nonanone enhanced avoidance of nonanone. This plasticity was independent of the presence of food during pre-exposure and required dopamine, which plays an important role in human behavioral plasticity. (5) Genetic theory on parallel pathways. The genetic theory that derives the order of genes in signaling pathways from epistasis data was expanded to the cases of parallel pathways. The new theory succeeded in explaining a certain enigmatic phenomenon.