Live imaging of apoptosis in a novel transgenic mouse highlights its role in neural tube closure.
Live imaging of apoptosis in a novel transgenic mouse highlights its role in neural tube closure.
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DOI：
10.1083/jcb.201104057
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发表时间：
2011-12-12
期刊：
影响因子：
--
通讯作者：
Miura M
中科院分区：
文献类型：
--
作者：
Yamaguchi Y;Shinotsuka N;Nonomura K;Takemoto K;Kuida K;Yosida H;Miura M
活体小鼠胚胎发育过程中caspase激活的成像表明，caspase介导的细胞移除以暂时调节的方式促进神经管闭合。许多细胞在发育、组织稳态和疾病过程中死亡。细胞凋亡的失调导致颅神经管闭合（NTC）缺陷，如畸形，尽管其机制尚不清楚。在生活环境中观察细胞凋亡可以帮助阐明其起源、行为和对周围组织的影响，但很少有工具可用于此目的，特别是在哺乳动物中。在本文中，我们利用绝缘子序列产生了一种转基因小鼠，该小鼠稳定表达了基于基因编码荧光共振能量转移（FRET）的caspase激活荧光报告基因，并对活胚胎的细胞凋亡和形态发生进行了同步延时成像。快速扫描共聚焦显微镜下的实时FRET成像显示，含有活化caspase的细胞在NTC期间以区域特异性的方式表现出典型和非典型的凋亡行为。抑制半胱天冬酶激活会干扰和延迟颅NTC的顺利进展，这可能会增加颅内畸形的风险。我们的研究结果表明，caspase介导的细胞去除有助于在有限的发育窗口内完成NTC。
Imaging of caspase activation in living mouse embryos during development suggests that caspase-mediated cell removal facilitates neural tube closure in a temporally regulated manner. Many cells die during development, tissue homeostasis, and disease. Dysregulation of apoptosis leads to cranial neural tube closure (NTC) defects like exencephaly, although the mechanism is unclear. Observing cells undergoing apoptosis in a living context could help elucidate their origin, behavior, and influence on surrounding tissues, but few tools are available for this purpose, especially in mammals. In this paper, we used insulator sequences to generate a transgenic mouse that stably expressed a genetically encoded fluorescence resonance energy transfer (FRET)–based fluorescent reporter for caspase activation and performed simultaneous time-lapse imaging of apoptosis and morphogenesis in living embryos. Live FRET imaging with a fast-scanning confocal microscope revealed that cells containing activated caspases showed typical and nontypical apoptotic behavior in a region-specific manner during NTC. Inhibiting caspase activation perturbed and delayed the smooth progression of cranial NTC, which might increase the risk of exencephaly. Our results suggest that caspase-mediated cell removal facilitates NTC completion within a limited developmental window.
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DOI：
10.1083/jcb.200905110
发表时间：
2009-10-19
期刊：
The Journal of cell biology
影响因子：
--
作者：
Koto A;Kuranaga E;Miura M
通讯作者：
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通讯作者：
Tsai, TF
DOI：
10.1083/jcb.201004096
发表时间：
2010-06-28
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Ravichandran KS
DOI：
10.1002/tera.1420470112
发表时间：
1993-01-01
期刊：
TERATOLOGY
影响因子：
--
作者：
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通讯作者：
CHERNOFF, GF