Wimmer E A, Jäckle H, Pfeifle C, Cohen S M
Howard Hughes Medical Institute, Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030.
Nature. 1993 Dec 16;366(6456):690-4. doi: 10.1038/366690a0.
Segmentation in Drosophila is based on a cascade of hierarchical gene interactions initiated by maternally deposited morphogens that define the spatially restricted domains of gap gene expression at blastoderm (reviewed in ref. 1). Although segmentation of the embryonic head is morphologically obscured, the repeated patterns of expression of the segment polarity genes reflect the formation of seven head segments; two of these depend on the segmentation and homeotic genes used in the trunk, whereas the others form as a result of the activity of the head-specific genes orthodenticle (otd), empty spiracles (ems) and buttonhead (btd). The genes ems and otd encode homeodomain proteins, suggesting that they may function as transcription factors. They are expressed in overlapping stripes in the early embryonic head of Drosophila, and their vertebrate homologues, otx and emx, are expressed in overlapping domains in the anterior central nervous system of the mouse embryo. We show here that btd is expressed in a stripe covering the head analgen of the segments affected in btd lack-of-function mutants and that btd encodes a zinc-finger-type transcription factor with sequence and functional similarity to the prototype mammalian transcription factor Sp1 (ref. 9). When expressed in the spatial pattern of btd, a transgene providing Sp1 activity can support development of the mandibular segment in the head of btd mutant embryos. A ubiquitous transcription factor from humans can therefore replace an essential component of the genetic circuitry required to specify the development of a particular head segment in the fly.
果蝇的体节形成基于一系列由母体沉积的形态发生素引发的层次基因相互作用,这些形态发生素在囊胚期定义了间隙基因表达的空间受限区域(参考文献1中有综述)。尽管胚胎头部的体节形成在形态上不明显,但体节极性基因的重复表达模式反映了七个头部体节的形成;其中两个依赖于躯干中使用的体节和同源异型基因,而其他的则是由于头部特异性基因正齿(otd)、空气门(ems)和纽扣头(btd)的活性而形成。基因ems和otd编码同源结构域蛋白,这表明它们可能作为转录因子发挥作用。它们在果蝇早期胚胎头部以重叠条纹的形式表达,并且它们的脊椎动物同源物otx和emx在小鼠胚胎的前中枢神经系统中以重叠结构域的形式表达。我们在此表明,btd在一条覆盖btd功能缺失突变体中受影响体节的头部原基的条带中表达,并且btd编码一种锌指型转录因子,其序列和功能与原型哺乳动物转录因子Sp1相似(参考文献9)。当以btd的空间模式表达时,提供Sp1活性的转基因可以支持btd突变体胚胎头部下颌体节的发育。因此,来自人类的一种普遍存在的转录因子可以替代果蝇中指定特定头部体节发育所需遗传回路的一个必需成分。