Svendsen P C, Marshall S D, Kyba M, Brook W J
Department of Biochemistry and Molecular Biology, and Genes and Development Research Group, Faculty of Medicine, University of Calgary, Calgary Alberta, T2N 4N1, Canada.
Development. 2000 Oct;127(19):4083-93. doi: 10.1242/dev.127.19.4083.
The combgap locus, first described by C. B. Bridges in 1925, is a gene required for proper anteroposterior pattern formation in the limbs of Drosophila melanogaster. The development of the anteroposterior axis of fly limbs is initiated by hedgehog signaling from cells of the posterior half to cells of the anterior half of the limb primordium. Hedgehog signaling requires the anterior-specific expression of the gene cubitus interruptus to establish posterior-specific hedgehog secretion and anterior-specific competence to respond to hedgehog. We have cloned combgap and find that it encodes a chromosomal protein with 11 C(2)H(2) zinc fingers. Limb defects found in combgap mutants consist of either loss or duplication of pattern elements in the anteroposterior axis and can be explained through the inappropriate expression of cubitus interruptus and its downstream target genes. In combgap mutants, cubitus interruptus is ectopically expressed in the posterior compartments of wing imaginal discs and is downregulated in the anterior compartment of legs, wings and antennae. We are able to rescue anterior compartment combgap phenotypes by expressing additional cubitus interruptus using the Gal4/UAS system. Dominant alleles of cubitus interruptus, which result in posterior expression, phenocopy combgap posterior compartment phenotypes. Finally, we find that the combgap protein binds to polytene chromosomes at many sites including the cubitus interruptus locus, suggesting that it could be a direct regulator of cubitus interruptus transcription.
梳隙基因座由C. B. 布里奇斯于1925年首次描述，是黑腹果蝇肢体前后模式正确形成所需的一个基因。果蝇肢体前后轴的发育由肢体原基后半部分细胞向其前半部分细胞发出的刺猬信号启动。刺猬信号需要基因间断翅脉在前部特异性表达，以建立后部特异性刺猬分泌以及前部特异性的响应刺猬信号的能力。我们克隆了梳隙基因，发现它编码一种具有11个C(2)H(2)锌指的染色体蛋白。在梳隙基因突变体中发现的肢体缺陷包括前后轴上模式元件的缺失或重复，这可以通过间断翅脉及其下游靶基因的异常表达来解释。在梳隙基因突变体中，间断翅脉在翅成虫盘的后部区域异位表达，而在腿、翅和触角的前部区域表达下调。我们能够通过使用Gal4/UAS系统表达额外的间断翅脉来挽救前部区域的梳隙基因表型。导致后部表达的间断翅脉显性等位基因模拟梳隙基因后部区域的表型。最后，我们发现梳隙蛋白在包括间断翅脉基因座在内的多个位点与多线染色体结合，这表明它可能是间断翅脉转录的直接调节因子。
