Newby L M, Jackson F R
Neurobiology Group, Worcester Foundation For Experimental Biology, Shrewsbury, Massachusetts 01545.
Genetics. 1993 Dec;135(4):1077-90. doi: 10.1093/genetics/135.4.1077.
To identify components of a circadian pacemaker output pathway, we have sought Drosophila mutations that alter the timing of eclosion but do not perturb circadian period or the expression of the activity rhythm. A mutant named lark has been identified, for which daily peaks of eclosion occur abnormally early while populations are synchronized to either light/dark or temperature cycles. The temporal phasing of locomotor activity in lark mutants, however, is entirely normal, as is the free-running period of the circadian pacemaker. The lark strain carries a single P-element insertion which, interestingly, has a dominant effect on the timing of eclosion, but is also associated with a recessive embryonic lethal phenotype. The analysis of excision-generated alleles suggests that the lark gene encodes an essential function. This function is apparently mediated by a transcription unit that is interrupted by the P-induced lark mutation. A combination of in situ hybridization analysis and reporter (beta-gal) staining indicates that this transcription unit expresses mRNAs throughout the embryonic central nervous system and in a defined subset of cells in the nervous system of pharate adults. RNAs are first detected at about embryonic stage 11, just prior to the stage at which lethality occurs in lark homozygotes. Based primarily on the observed mutant phenotypes, a function is proposed for the LARK product(s) that is consistent with the pleiotropic nature of lark mutations.
为了确定昼夜节律起搏器输出通路的组成部分，我们寻找了能改变羽化时间但不干扰昼夜节律周期或活动节律表达的果蝇突变体。已鉴定出一个名为lark的突变体，在群体同步于光/暗或温度循环时，其羽化的每日峰值异常提前出现。然而，lark突变体中运动活动的时间相位是完全正常的，昼夜节律起搏器的自由运行周期也是如此。lark品系携带一个单一的P因子插入，有趣的是，它对羽化时间有显性作用，但也与隐性胚胎致死表型相关。对切除产生的等位基因的分析表明，lark基因编码一种基本功能。这种功能显然由一个转录单元介导，该转录单元被P诱导的lark突变打断。原位杂交分析和报告基因（β-半乳糖苷酶）染色相结合表明，这个转录单元在整个胚胎中枢神经系统以及在即将羽化的成虫神经系统的特定细胞亚群中表达mRNA。RNA最早在胚胎发育第11阶段左右被检测到，就在lark纯合子出现致死性的阶段之前。主要基于观察到的突变体表型，提出了与lark突变的多效性性质一致的LARK产物的功能。
