Molecular Biological Analyses of the Neural Functions of the Nematode C. elegans

我们利用分子生物学方法，以线虫线虫为研究对象，研究了线虫行为的遗传基础。(A)第一类flr基因与抗氟离子、生长速度、排便周期和感官信号的处理有关，编码一个离子通道、一个蛋白激酶和一个类似于激酶的分子。在这项研究中，我们证明了它们构成了一个在肠道中起作用的调节系统，并调节了许多与食物相关的功能。Flr-2基因位于调控系统的下游，编码在某些神经元中表达的分泌蛋白。(B)SDF-13基因编码一种与哺乳动物Tbx2同源的转录因子，是某些气味的趋化性适应所必需的，通过人工合成的Dauer构成突变来鉴定。(C)ut236突变基因编码具有LDLa结构域的分泌蛋白，是正常联想学习所必需的，它使铜离子优先于气味趋化性。Ut235突变体在饥饿使铜离子回避减敏的反应中存在异常。(D)感觉纤毛延伸所需的CHE-2基因编码一种具有WD40重复序列的新蛋白，该蛋白定位于纤毛。使用CHE-2克隆，我们成功地恢复了CHE-2突变体的部分感觉神经元或任何发育阶段的CHE-2功能。这项实验揭示了感官纤毛的动态性质。所有这些研究表明，可以用分子生物学方法在分子和细胞水平上分析行为，这些研究带来了新的发现。

We studied the genetic basis of behavior by molecular biological methods, using the nematode C. elegans. (a) The class 1 flr genes, which are related to resistance to fluoride ion, growth rates, defecation cycle periods and the processing of sensory signals, encode an ion channel, a protein kinase and a kinase-like molecule. In this study we showed that they constitute a regulatory system that acts in the intestine and that regulates many food-related functions. The flr-2 gene, which is located in the downstream of the regulatory system, encoded a secretary protein expressed in certain neurons. (b) The sdf-13 gene, which is identified by synthetic dauer-constitutive mutations, encoded a transcriptional factor homologous to the mammalian Tbx2 and was required for the adaptation of chemotaxis to certain odorants. (c) The gene for the ut236 mutation, which confers preference of copper ion over chemotaxis to odorants, encoded a secretory protein having an LDLa domain and was required for normal associative learning. The ut235 mutant had abnormality in the response in which starvation desensitizes the avoidance of copper ion. (d) The che-2 gene, which is required for the extension of sensory cilia, encoded a novel protein that has WD40 repeats and that is localized at cilia. Using the che-2 clone, we succeeded in restoring the che-2 function in a subset of sensory neurons or at any stage of development in che-2 mutants. This experiment revealed a dynamic nature of sensory cilia. All these studies demonstrated that behavior can be analyzed at molecular and cellular levels by molecular biological methods and that such studies lead to new discoveries.