Benitez Sergio, Sosa Claudia, Tomasini Nicolás, Macías Ana
Facultad de Ciencias Exactas Físicas y Naturales de la Universidad Nacional de Córdoba, Córdoba, Argentina.
Int J Dev Biol. 2010;54(4):643-53. doi: 10.1387/ijdb.082724sb.
Apoptosis is necessary for the regulation of growth during development, but the precise details of this regulation have not been completely characterized. In this study, we used the Drosophila genital disc as a model to analyze the contribution of apoptosis to growth regulation. We studied the expression or activity of several elements of the apoptotic death pathway such as Drosophila inhibitor of apoptosis1, caspases, the apoptotic genes reaper (rpr) and head involution defective, as well as elements of the Jun-NH2-terminal kinase (JNK) pathway. We found that the JNK pathway is active in a dynamic, asymmetric and genitalia-specific manner. Apoptosis, as measured in terms of the expression of a variety of apoptotic molecules, occurs in a JNK-dependent and -independent manner and was detected among engrailed (en) expressing cells. JNK regulation of apoptotic genes is necessary to control growth in both sexes and rotation in males; this regulatory role is necessary to execute en(+) cell death and to activate expression of rpr in these cells. rpr is up-regulated at antero-posterior borders, and this expression appears to be of particular importance in the control of growth, since the balance between cell proliferation and death in those regions appears to depend on the equilibrium between pro- and anti-apoptotic factors at a cellular level.
细胞凋亡对于发育过程中的生长调节是必要的,但这种调节的确切细节尚未完全明确。在本研究中,我们以果蝇生殖盘为模型来分析细胞凋亡对生长调节的作用。我们研究了凋亡死亡途径的几个元件的表达或活性,如果蝇凋亡抑制因子1、半胱天冬酶、凋亡基因收割者(rpr)和头部内卷缺陷基因,以及Jun-NH2-末端激酶(JNK)途径的元件。我们发现JNK途径以动态、不对称且特定于生殖器的方式激活。以多种凋亡分子的表达来衡量,细胞凋亡以依赖和不依赖JNK的方式发生,并在表达 engrailed(en)的细胞中被检测到。JNK对凋亡基因的调节对于控制两性的生长和雄性的旋转是必要的;这种调节作用对于执行en(+)细胞死亡以及激活这些细胞中rpr的表达是必要的。rpr在前后边界处上调,并且这种表达在生长控制中似乎特别重要,因为这些区域中细胞增殖与死亡之间的平衡似乎取决于细胞水平上促凋亡和抗凋亡因子之间的平衡。