MOLECULAR BIOLOGICAL ANALYSES OF THE BEHAVIORS OF THE NEMATODE C.ELEGANS

以线虫线虫为研究对象，研究了线虫行为的遗传基础。(A)对合成Dauer结构突变体的研究产生了以下结果。Tbx2转录因子同源功能在AWC感觉神经元嗅觉适应中的作用酪氨酸磷酸酶同系物SDF-13在功能未知的XXXL/R细胞中参与类固醇激素代谢。多药耐药相关蛋白同源物MRP-1在调节肠道、咽部和神经系统达尔幼虫的形成中发挥作用，而人MRP1可以替代线虫MRP-1发挥这一作用。(B)导致生长、排便和感觉功能异常的1类flr突变和抑制某些1类表型的2类flr突变。新的2类突变被分离出来，作为1类突变的5-羟色胺敏感性抑制因子。2类突变体的寿命较短。(C)HEN-1突变体在学习温度和饥饿方面也表现出异常，该突变体更喜欢避免铜离子而不是趋化性气味。在成体阶段，HEN-1基因在两对神经元中以非细胞自主方式发挥作用。HEN-1中的一个缺失突变体表现出与原始错义等位基因ut236基本相同的表型。(D)动物经食物和丁酮处理后，对丁酮的趋化性增强，并分离到这种行为异常的突变株。其中一个菌株ut305对苯甲醛和异戊醇的适应性也不正常。Ut305基因编码一种新的膜蛋白，在许多咽神经元和AIA中间神经元中都有表达。(E)研究长期暴露于有害刺激后的行为变化。根据这些结果，很明显，许多行为是由食物和饥饿的信号通过多条途径调节的。这是揭示线虫行为中枢控制机制的重要线索。

The genetic basis of behavior was studied by using the nematode C.elegans. (a) Studies on synthetic dauer-constitutive mutants yielded the following results. The Tbx2 transcription factor homologue function's in olfactory adaptation in AWC sensory neurons. The Tyr-phosphatase homologue SDF-13 acts in steroid hormone metabolism in XXXL/R cells whose function had been unknown. The multidrug resistance-associated protein homologue MRP-1 plays a role in the regulation of dauer larva formation in the intestine, pharynx and nervous system, while human MRP1 can substitute for C.elegans MRP-1 in this function. (b) Class 1 flr mutations, which confer abnormality in growth, defecation and sensory functions, and class 2 flr mutations, which suppress some of the class 1 phenotypes were investigated. New class 2 mutations were isolated as suppressors serotonin-sensitivity of class 1 mutations. Class 2 mutants showed shorter longevity. (c) hen-1 mutants, which prefer avoidance of copper ion to chemotaxis to odorants, showed abnormality also in the learning of temperature and starvation. hen-1 gene functions non-cell-autonomously in two pairs of neurons at the adult stage. A deletion mutant in hen-1 showed essentially the same phenotype as the original missense allele ut236. (d) Animals showed increased chemotaxis to butanone after conditioning with food and butanone, and mutants abnormal in this behavior were isolated. One of them, ut305, was also abnormal in adaptation to benzaldehyde and isoamyl alcohol. Th ut305 gene encoded a novel membrane protein and was expressed in many pharyngeal neurons and AIA interneurons. (e) Changes of behavior after prolonged exposure to noxious stimuli were studied. On the basis of these results, it has become clear that many behaviors are regulated by signals of food and starvation through multiple pathways. This is an important clue to the central control mechanism of behavior in C.elegans.