Abraham Mary C, Lu Yun, Shaham Shai
Laboratory of Developmental Genetics, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Dev Cell. 2007 Jan;12(1):73-86. doi: 10.1016/j.devcel.2006.11.012.
Apoptosis, cell death characterized by stereotypical morphological features, requires caspase proteases. Nonapoptotic, caspase-independent cell death pathways have been postulated; however, little is known about their molecular constituents or in vivo functions. Here, we show that death of the Caenorhabditis elegans linker cell during development is independent of the ced-3 caspase and all known cell death genes. The linker cell employs a cell-autonomous death program, and a previously undescribed engulfment program is required for its clearance. Dying linker cells display nonapoptotic features, including nuclear crenellation, absence of chromatin condensation, organelle swelling, and accumulation of cytoplasmic membrane-bound structures. Similar features are seen during developmental death of neurons in the vertebrate spinal cord and ciliary ganglia. Linker cell death is controlled by the microRNA let-7 and Zn-finger protein LIN-29, components of the C. elegans developmental timing pathway. We propose that the program executing linker cell death is conserved and used during vertebrate development.
凋亡是一种以典型形态学特征为特点的细胞死亡方式，需要半胱天冬酶蛋白酶的参与。非凋亡性、不依赖半胱天冬酶的细胞死亡途径已被提出；然而，对于它们的分子组成或体内功能却知之甚少。在此，我们表明秀丽隐杆线虫发育过程中连接细胞的死亡不依赖于ced-3半胱天冬酶和所有已知的细胞死亡基因。连接细胞采用细胞自主死亡程序，并且其清除需要一个先前未描述的吞噬程序。濒死的连接细胞表现出非凋亡特征，包括核皱缩、染色质不凝聚、细胞器肿胀以及细胞质膜结合结构的积累。在脊椎动物脊髓和睫状神经节神经元的发育性死亡过程中也观察到类似特征。连接细胞死亡受微小RNA let-7和锌指蛋白LIN-29控制，它们是秀丽隐杆线虫发育时间调控途径的组成部分。我们提出执行连接细胞死亡的程序在脊椎动物发育过程中是保守的且被使用。
