Genetic screens for Caenorhabditis elegans mutants defective in left/right asymmetric neuronal fate specification
Genetic screens for Caenorhabditis elegans mutants defective in left/right asymmetric neuronal fate specification
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DOI：
10.1534/genetics.107.075648
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发表时间：
2007-08-01
期刊：
影响因子：
3.3
通讯作者：
Hobert, Oliver
中科院分区：
文献类型：
--
作者：
Sarin, Sumeet;O'Meara, M. Maggie;Hobert, Oliver
我们在这里描述的结果遗传筛选秀丽隐杆线虫突变体中，一个单一的神经元的命运决定是不适当的执行。在野生型动物中，两个形态学上双侧对称的味觉神经元ASE左（ASEL）和ASE右（ASER）经历了细胞命运的左/右不对称多样化，表现为一类推定的化学感受器和神经肽的差异表达。使用单细胞特异性gfp报告基因并通过总共近120，000个单倍体基因组进行筛选，我们分离出161个突变体，这些突变体定义了至少六种不同类型的突变体表型，其中ASEL/R命运被破坏。每个突变体表型类别包括1至9个不同的互补组。除了许多等位基因的10个先前描述的基因，我们已经确定了至少16个新的“lsy”基因（“横向对称”）。在已知基因的突变中，我们检索到了miRNA lsy-6的四个等位基因和lsy-6靶基因（cog-1同源框基因）3 '-UTR中的一个功能获得性突变。使用新发现的cog-1的温度敏感等位基因，我们确定了一个控制ASEL与ASER命运的温度反馈环，其中cog-1是一个组成部分，只是暂时需要启动，而不是维持ASEL和ASER命运。总之，我们的突变体筛选确定了一个广泛的基因目录，其分子特征预计将提供更多的了解左/右不对称神经元细胞命运决定的复杂遗传结构。
We describe here the results of genetic screens for Caenorhabdilis elegans mutants in which a single neuronal fate decision is inappropriately executed. In wild-type animals, the two morphologically bilaterally symmetric gustatory neurons ASE left (ASEL) and ASE right (ASER) undergo a left/right asymmetric diversification in cell fate, manifested by the differential expression of a class of putative chemoreceptors and neuropeptides. Using single cell-specific gfp reporters and screening through a total of almost 120,000 haploid genomes, we isolated 161 mutants that define at least six different classes of mutant phenotypes in which ASEL/R fate is disrupted. Each mutant phenotypic class encompasses one to nine different complementation groups. Besides many alleles of 10 previously described genes, we have identified at least 16 novel "lsy" genes ("laterally symmetric"). Among mutations in known genes, we retrieved four alleles of the miRNA lsy-6and a gain-of-function mutation in the 3'-UTR of a target of lsy-6, the cog-1 homeobox gene. Using newly found temperature-sensitive alleles of cog-1, we determined that a bistable feedback loop controlling ASEL vs. ASER fate, of which cog-l is a component, is only transiently required to initiate but not to maintain ASEL and ASER fate. Taken together, our mutant screens identified a broad catalog of genes whose molecular characterization is expected to provide more insight into the complex genetic architecture of a left/right asymmetric neuronal cell fate decision.