Fujioka Miki, Wessells Robert J, Han Zhe, Liu Jiandong, Fitzgerald Kerry, Yusibova Galina L, Zamora Monica, Ruiz-Lozano Pilar, Bodmer Rolf, Jaynes James B
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Circ Res. 2005 Nov 25;97(11):1108-14. doi: 10.1161/01.RES.0000191546.08532.B2. Epub 2005 Oct 20.
The Drosophila pair-rule gene even skipped (eve) is required for embryonic segmentation and later in specific cell lineages in both the nervous system and the mesoderm. We previously generated eve mesoderm-specific mutants by combining an eve null mutant with a rescuing transgene that includes the entire locus, but with the mesodermal enhancer removed. This allowed us to analyze in detail the defects that result from a precisely targeted elimination of mesodermal eve expression in the context of an otherwise normal embryo. Absence of mesodermal eve causes a highly selective loss of the entire eve-expressing lineage in this germ layer, including those progeny that do not continue to express eve, suggesting that mesodermal eve precursor specification is not implemented. Despite the resulting absence of a subset of muscles and pericardial cells, mesoderm-specific eve mutants survive to fertile adulthood, providing an opportunity to examine the effects of these developmental abnormalities on adult fitness and heart function. We find that in these mutants, flying ability, myocardial performance under normal and stressed conditions, and lifespan are severely reduced. These data imply a nonautonomous role of the affected pericardial cells and body wall muscles in developing and/or maintaining cardiac performance and possibly other functions contributing to normal lifespan. Given the similarities of molecular-genetic control between Drosophila and vertebrates, these findings suggest that peri/epicardial influences may well be important for proper myocardial function.
果蝇的成对规则基因even skipped（eve）对于胚胎分割以及随后神经系统和中胚层特定细胞谱系的发育是必需的。我们之前通过将eve无效突变体与一个拯救转基因相结合，构建了eve中胚层特异性突变体，该转基因包含整个基因座，但中胚层增强子已被去除。这使我们能够在其他方面正常的胚胎背景下，详细分析中胚层eve表达被精确靶向消除所导致的缺陷。中胚层eve的缺失导致该胚层中整个表达eve的细胞谱系高度选择性丧失，包括那些不再继续表达eve的后代，这表明中胚层eve前体的特化并未实现。尽管导致了一部分肌肉和心包细胞缺失，但中胚层特异性eve突变体仍能存活至成年并具有繁殖能力，这为研究这些发育异常对成年适应性和心脏功能的影响提供了机会。我们发现，在这些突变体中，飞行能力、正常和应激条件下的心肌性能以及寿命都严重降低。这些数据表明，受影响的心包细胞和体壁肌肉在发育和/或维持心脏性能以及可能对正常寿命有贡献的其他功能中具有非自主性作用。鉴于果蝇和脊椎动物在分子遗传控制方面的相似性，这些发现表明围心/心包的影响对于正常心肌功能可能非常重要。
