Chouinard S, Kaufman T C
Howard Hughes Medical Institute, Indiana University, Bloomington 47405.
Development. 1991 Dec;113(4):1267-80. doi: 10.1242/dev.113.4.1267.
The homeotic gene labial (lab) is required for proper development of the embryonic and adult head in Drosophila melanogaster. The lab gene product accumulates in a complex pattern in both embryonic and imaginal tissue. During embryogenesis, lab is expressed in the endodermally derived cells of the midgut, in ectodermally derived cells of the procephalon and dorsal ridge, and in a small subset of progenitor sensory cells. Imaginal expression is restricted to a narrow region of the peripodial membrane of the eye-antennal disc. As part of our continuing effort to understand the role of lab in development, we have begun a dissection of the regulatory elements of the lab transcription unit and used germ line transformation experiments to determine which aspects of the observed expression pattern are essential for proper head development and viability. Transgenic embryos harboring an abridged lab gene are able to overcome the embryonic lethality associated with the loss of lab function and survive to adulthood. Interestingly, in these transgenic lines the lab protein accumulates only in a subset of those embryonic cells that normally express the gene, namely the procephalon and the anterior midgut. We also find that, once initiated, lab expression is maintained by positive autoregulation. Although lab minigene activity is sufficient to rescue the embryonic lethality of lab mutations, the transgenes fail to rescue defects in the adult head capsule. However, the defects observed in this study encompass a broader domain than those seen using somatic recombination to generate lab- clonal tissue. The failed rescue and observed cuticular defects are, at least in part, explained by the observation that the transgenes, rather than failing to be expressed, are associated with ectopic accumulation of lab protein in the peripodial membrane of the antennal disc. Moreover, this aberrant expression pattern is correlated with the abnormal expression of two other homeotic genes, Deformed (Dfd) and Sex combs reduced (Scr) in the eye-antennal disc. These results are only observed when the transgene is resident in a lab- genotype and ectopic expression of lab and misregulation of Dfd and Scr are not seen in a lab+ background. This result suggests that the wild-type lab gene product is necessary for the normal regulation of the locus in the imaginal discs, but unlike the case in the embryo, the event is negative. We discuss the biological implications of these results in relation to the role of lab in development.
同源异型基因唇（lab）对于黑腹果蝇胚胎和成体头部的正常发育是必需的。lab基因产物在胚胎组织和成虫盘组织中以复杂的模式积累。在胚胎发生过程中，lab在中肠内胚层来源的细胞、前脑和背嵴外胚层来源的细胞以及一小部分祖细胞感觉细胞中表达。成虫盘表达局限于眼触角盘围膜的一个狭窄区域。作为我们持续努力理解lab在发育中作用的一部分，我们开始剖析lab转录单元的调控元件，并利用种系转化实验来确定观察到的表达模式的哪些方面对于正常头部发育和生存能力是必不可少的。携带截短lab基因的转基因胚胎能够克服与lab功能丧失相关的胚胎致死性并存活至成年。有趣的是，在这些转基因品系中，lab蛋白仅在那些正常表达该基因的胚胎细胞的一个子集中积累，即前脑和中肠前部。我们还发现，一旦启动，lab表达通过正向自调控得以维持。尽管lab小基因活性足以挽救lab突变的胚胎致死性，但转基因未能挽救成虫头壳的缺陷。然而，本研究中观察到的缺陷比使用体细胞重组产生lab克隆组织时所见涵盖更广泛的区域。未能挽救以及观察到的表皮缺陷至少部分可以通过以下观察结果来解释：转基因并非未能表达，而是与lab蛋白在触角盘围膜中的异位积累相关。此外，这种异常表达模式与眼触角盘中另外两个同源异型基因变形（Dfd）和性梳减少（Scr）的异常表达相关。这些结果仅在转基因存在于lab基因型时观察到，在lab +背景中未见到lab的异位表达以及Dfd和Scr的调控异常。这一结果表明，野生型lab基因产物对于成虫盘中该位点的正常调控是必需的，但与胚胎情况不同，该事件是负向的。我们讨论了这些结果与lab在发育中的作用相关的生物学意义。
