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

我们对食物、饥饿和驱虫剂在秀丽隐杆线虫学习行为和其他功能中的作用进行了遗传和分子生物学研究，得到了以下结果。(1)用丁酮和食物学习。我们发现预先暴露于丁酮和食物会特别增强对丁酮的趋化性，并分析了这种行为的突变体。这种行为需要Bardet-Biedl综合征基因在AWC-ON神经元感觉纤毛上的功能，AWC-ON神经元感知丁酮。它还需要G α蛋白ODR-3中特定的氨基酸残基，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)控制肠道生长速率等。我们对控制肠道生长速率等的1类flr基因进行了基因内分析。2类flr基因可以中和1类基因，也可以调节对大肠杆菌的免疫力。其中一个基因flr-2编码了DAN/Gremlin/Cerberus家族的分泌蛋白，该蛋白在神经元中表达。我们发现了flr -2结合蛋白ZK20.1，该蛋白调节排便周期。(3)大鼠幼虫调控分析。我们研究了大量关于已知突变的合成dauer构成表型的数据，它们被另一个突变抑制，以及dauer信号分子DAF-7在各种突变背景下的表达。(4)预暴露于驱避气味后的行为改变。预暴露于壬甲酮增强了对壬甲酮的回避。这种可塑性不依赖于暴露前食物的存在和所需的多巴胺，而多巴胺在人类的行为可塑性中起着重要作用。(5)平行路径的遗传理论。从上位性数据推导信号通路中基因顺序的遗传理论扩展到平行通路的情况。新理论成功地解释了某种神秘的现象。

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.