Mace Kimberly, Tugores Antonio
Surgical Research Lab, University of California, San Francisco, Box 1302, San Francisco, CA 94143-1302, USA.
BMC Dev Biol. 2004 Dec 13;4:15. doi: 10.1186/1471-213X-4-15.
The Drosophila split ends (spen) gene encodes a large nuclear protein containing three RNP-type RNA binding motifs, and a conserved transcriptional co-repressor-interacting domain at the C-terminus. Genetic analyses indicate that spen interacts with pathways that regulate the function of Hox proteins, the response to various signaling cascades and cell cycle control. Although spen mutants affect only a small subset of morphological structures in embryos, it has been difficult to find a common theme in spen mutant structural alterations, or in the interactions of spen with known signaling pathways.
By generating clones of spen mutant cells in wing imaginal discs, we show that spen function is required for the correct formation and positioning of veins and mechanosensory bristles both on the anterior wing margin and on the notum, and for the maintenance of planar polarity. Wing vein phenotypic alterations are enhanced by mutations in the crinkled (ck) gene, encoding a non-conventional myosin, and correlate with an abnormal spatial expression of Delta, an early marker of vein formation in third instar wing imaginal discs. Positioning defects were also evident in the organization of the embryonic peripheral nervous system, accompanied by abnormal E-Cadherin expression in the epidermis.
The data presented indicate that the role of spen is necessary to maintain the correct positioning of cells within a pre-specified domain throughout development. Its requirement for epithelial planar polarity, its interaction with ck, and the abnormal E-Cadherin expression associated with spen mutations suggest that spen exerts its function by interacting with basic cellular mechanisms required to maintain multicellular organization in metazoans. This role for spen may explain why mutations in this gene interact with the outcome of multiple signaling pathways.
果蝇的“分裂末端”(spen)基因编码一种大型核蛋白,该蛋白包含三个RNP型RNA结合基序,以及位于C端的一个保守的转录共抑制因子相互作用结构域。遗传分析表明,spen与调节Hox蛋白功能、对各种信号级联反应的应答以及细胞周期控制的信号通路相互作用。尽管spen突变体仅影响胚胎中一小部分形态结构,但很难在spen突变体的结构改变或spen与已知信号通路的相互作用中找到共同规律。
通过在翅成虫盘上产生spen突变体细胞克隆,我们发现spen功能对于前翅边缘和背板上静脉和机械感觉刚毛的正确形成和定位以及平面极性的维持是必需的。编码非常规肌球蛋白的“皱缩”(ck)基因突变会增强翅静脉表型改变,且这与Delta的异常空间表达相关,Delta是三龄翅成虫盘中静脉形成的早期标记物。定位缺陷在胚胎外周神经系统的组织中也很明显,同时伴随着表皮中E-钙黏蛋白的异常表达。
所呈现的数据表明,spen的作用对于在整个发育过程中维持细胞在预定区域内的正确定位是必要的。它对上皮平面极性的要求、与ck的相互作用以及与spen突变相关的E-钙黏蛋白异常表达表明,spen通过与维持后生动物多细胞组织所需的基本细胞机制相互作用来发挥其功能。spen的这一作用可能解释了为什么该基因的突变会与多种信号通路的结果相互作用。