Role of Signal-transduction in the Development of C.elegans

线虫的抗氟（flr）突变都是隐性的，包括两类。1类突变（flr-1、flr-3和flr-4）赋予蠕虫强抗性和缓慢生长，而2类突变（flr-2和flr-5）赋予弱抗性，保持生长速率不变并抑制1类突变的缓慢生长表型。在本研究中，我们定位了2类突变，并在这些突变和包括它的缺陷之间制造了杂合子，杂合子的表型表明所有的2类突变都是亚型或无效突变。我们还进行了flr突变和一些已知突变之间的互补测试，这证实了它们定位在新基因中。flr基因可能在神经功能中起作用，因为这些基因的突变在某些情况下会影响dauer幼虫的形成。我们克隆了两个flr基因，flr-1和flr-3，以及它们的cDNA（不完整长度）。测序研究表明， ...更多信息 在推导的氨基酸序列中，FLR-1与某些离子通道具有弱同源性，而FLR-3很可能编码一个新家族的蛋白激酶。由于我们获得了两种在5'端区域不同的flr-3 cDNA，flr-3的表达可能受选择性剪接的调控。clr-1样突变是指导致幼虫肠外表面与体壁内表面分离的致死性突变。它们定位于已知的信号转导基因（let-23、let-341、let-60、lin-45、sem-5、lag-2、clr-1等）。未知的基因我们认为后者是信号转导系统的成员，或者它们在信号转导系统下游的细胞分化或细胞功能中起作用。在本研究中，我们克隆了一个4.4kb的DNA片段，其中包含let（ut 102），clr-1样突变的未知基因之一。我们正在对克隆进行测序，但到目前为止还没有发现与已知基因的同源性。我们计划研究该基因在蠕虫中的表达位置，以寻找致死突变的靶点。我们还将通过检查信号转导突变引起的let（ut 102）基因表达的变化以及通过将克隆显微注射到突变蠕虫中来测试突变的抑制来寻找let（ut 102）基因与已知信号转导系统之间的关系。少

The fluoride-resistant (flr) mutations of the nematode C.elegans are all recessive and consist of two classes. Class 1 mutations (flr-1, flr-3 and flr-4) confer strong resistance and slow growth on worms, whereas class 2 mutations (flr-2 and flr-5) confer weak resistance, keep the growth rate unchanged and suppress the slow-growing phenotype of class 1 mutations. In this study we mapped the class 2 mutations and made heterozygotes between either of these mutations and a deficiency including it. The phenotypes of the heterozygotes showed that all the class 2 mutations are hypomorphs or null mutations. We also performed complementation tests between the flr mutations and some known mutations, which confirmed that they map in new genes. The flr genes probably act in neural functions, because mutations in these genes affect formation of dauer larvae under certain circumstances. We cloned two of the flr genes, flr-1 and flr-3, and their cDNA (incomplete length). Sequencing studies showed th … More at the deduced amino acid sequence of flr-1 has weak homology to some ion channels, whereas flr-3 most probably codes for a protein kinase of a new family. Since we obtained two kinds of flr-3 cDNAs differing in the 5' region, the expression of flr-3 may be regulated by alternative splicing.The "clr-1-like" mutations are defined as larval lethal mutations that cause detachment of the outer surface of the intestine from the inner surface of the body wall. They map in known signal-transduction genes (let-23, let-341, let-60, lin-45, sem-5, lag-2, clr-1 etc.) and unknown genes. We think the latter genes are members of the signal-transduction systems, or they act in cell-differentiation or cell-functions downstream to the signal-transduction systems. In this study we cloned a 4.4kb DNA fragment that contains let(ut102), one of the unknown genes for the clr-1-like mutations. We are sequencing the clone, but homology to known genes has not been detected so far. We plan to study the position of expression of the gene in worms to look for the target of the lethal mutation. We will also search for the relation between the let(ut102) gene and known signal-transduction systems by checking change of its expression by signal-transduction mutations and by testing suppression of the mutations by microinjection of the clone into the mutant worms. Less