Nguyen Hanh T, Voza Francesca, Ezzeddine Nader, Frasch Manfred
Department of Medicine, Division of Cardiology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
J Cell Biol. 2007 Oct 22;179(2):219-27. doi: 10.1083/jcb.200708135.
We report that the Drosophila mind bomb2 (mib2) gene is a novel regulator of muscle development. Unlike its paralogue, mib1, zygotic expression of mib2 is restricted to somatic and visceral muscle progenitors, and their respective differentiated musculatures. We demonstrate that in embryos that lack functional Mib2, muscle detachment is observed beginning in mid stage 15 and progresses rapidly, culminating in catastrophic degeneration and loss of most somatic muscles by stage 17. Notably, the degenerating muscles are positive for apoptosis markers, and inhibition of apoptosis in muscles prevents to a significant degree the muscle defects. Rescue experiments with Mib1 and Neuralized show further that these E3 ubiquitin ligases are not capable of ameliorating the muscle mutant phenotype of mib2. Our data suggest strongly that mib2 is involved in a novel Notch- and integrin-independent pathway that maintains the integrity of fully differentiated muscles and prevents their apoptotic degeneration.
我们报告称,果蝇mind bomb2(mib2)基因是肌肉发育的一种新型调节因子。与其旁系同源基因mib1不同,mib2的合子表达仅限于体壁和内脏肌肉祖细胞及其各自分化的肌肉组织。我们证明,在缺乏功能性Mib2的胚胎中,从第15阶段中期开始观察到肌肉脱离,并迅速进展,最终在第17阶段导致大多数体壁肌肉灾难性退化和丧失。值得注意的是,退化的肌肉凋亡标记呈阳性,并且抑制肌肉中的凋亡在很大程度上可预防肌肉缺陷。用Mib1和Neuralized进行的拯救实验进一步表明,这些E3泛素连接酶无法改善mib2的肌肉突变体表型。我们的数据强烈表明,mib2参与了一条新的不依赖Notch和整合素的途径,该途径维持完全分化肌肉的完整性并防止其凋亡性退化。