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

以线虫为研究对象，研究了线虫行为的遗传基础。(a)对合成多肽组成突变体的研究产生了以下结果。Tbx2转录因子同源物在AWC感觉神经元嗅觉适应中的作用。酪氨酸磷酸酶同源物SDF-13参与XXXL/R细胞的类固醇激素代谢，其功能尚不清楚。多药耐药相关蛋白同源物MRP-1在肠、咽和神经系统中调控大鼠幼虫的形成，而人MRP1可以替代秀丽隐杆线虫的MRP-1发挥这一功能。(b)研究了导致生长、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类突变被分离为抑制1类突变的血清素敏感性。2类突变体寿命较短。(c)母鸡-1突变体更倾向于避开铜离子而不是对气味趋化，在温度和饥饿的学习上也表现出异常。Hen-1基因在成年期的两对神经元中非细胞自主地起作用。hen-1的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)经食物和丁酮调节后，动物对丁酮的趋化性增强，并分离出这种行为异常的突变体。其中，ut305对苯甲醛和异戊醇的适应也异常。ut305基因编码了一种新的膜蛋白，在许多咽神经元和AIA中间神经元中表达。(e)研究长时间暴露于有害刺激后的行为变化。基于这些结果，很明显，许多行为是由食物和饥饿信号通过多种途径调节的。这是研究秀丽隐杆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.