Nonautonomous Apoptosis Is Triggered by Local Cell Cycle Progression during Epithelial Replacement in Drosophila
Nonautonomous Apoptosis Is Triggered by Local Cell Cycle Progression during Epithelial Replacement in Drosophila
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DOI：
10.1128/mcb.01046-10
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发表时间：
2011-06-01
影响因子：
5.3
通讯作者：
Miura, Masayuki
中科院分区：
文献类型：
--
作者：
Nakajima, Yu-ichiro;Kuranaga, Erina;Miura, Masayuki
组织重塑涉及集体细胞运动，并且在发育和疾病中都观察到细胞增殖和凋亡。细胞凋亡和增殖被认为是密切相关的，但很少有人知道他们在体内生理组织重塑的协调调节。果蝇幼虫腹部表皮被成体表皮替代是组织重塑的一个简单模型。在此过程中，幼虫表皮细胞（LEC）经历凋亡，并被成体前体细胞--成组织细胞所取代。通过分析在单个细胞水平上的caspase激活，我们发现在LEC中的caspase激活在LEC/组织母细胞边界处被诱导，该边界随着LEC的死亡而扩大。操纵LEC/histoblast边界处的成组织细胞增殖，无论是遗传还是通过UV照射，表明与增殖的成组织细胞的局部相互作用触发边界LEC中的半胱天冬酶激活。最后，通过对体内成组织细胞S/G（2）/M期的时空动态监测，我们发现S/G（2）期的转变是在LEC/成组织细胞边界诱导非自主性LEC凋亡所必需的。替换边界，形成半胱天冬酶激活的细胞间通讯的局部调节，可以驱动组织重塑过程中的细胞替换的动态编排。
Tissue remodeling involves collective cell movement, and cell proliferation and apoptosis are observed in both development and disease. Apoptosis and proliferation are considered to be closely correlated, but little is known about their coordinated regulation in physiological tissue remodeling in vivo. The replacement of larval abdominal epidermis with adult epithelium in Drosophila pupae is a simple model of tissue remodeling. During this process, larval epidermal cells (LECs) undergo apoptosis and are replaced by histoblasts, which are adult precursor cells. By analyzing caspase activation at the single-cell level in living pupae, we found that caspase activation in LECs is induced at the LEC/histoblast boundary, which expands as the LECs die. Manipulating histoblast proliferation at the LEC/histoblast boundary, either genetically or by UV illumination, indicated that local interactions with proliferating histoblasts triggered caspase activation in the boundary LECs. Finally, by monitoring the spatiotemporal dynamics of the S/G(2)/M phase in histoblasts in vivo, we found that the transition from S/G(2) phases is necessary to induce nonautonomous LEC apoptosis at the LEC/histoblast boundary. The replacement boundary, formed as caspase activation is regulated locally by cell-cell communication, may drive the dynamic orchestration of cell replacement during tissue remodeling.