Apoptosis in metanephric development.
Apoptosis in metanephric development.
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跨跨性发育中的凋亡。
DOI：
10.1083/jcb.119.5.1327
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发表时间：
1992-12
期刊：
影响因子：
--
通讯作者：
al-Awqati Q
中科院分区：
文献类型：
--
作者：
Koseki C;Herzlinger D;al-Awqati Q
后肾发育过程中，非极化间充质细胞与输尿管芽组织产生的细胞外基质蛋白和因子相互作用后，被诱导形成肾元的上皮结构。这种诱导可以发生在跨滤器官培养系统中，它也可以由异源细胞如胚胎脊髓产生。我们发现，在体外和体内诱导胚胎间质时，新上皮周围的许多细胞表现出细胞核凝聚、细胞质破碎和细胞萎缩等程序性细胞死亡（凋亡）的形态学证据。细胞凋亡的生化关联是钙敏感内切酶的转录激活。事实上，从未诱导的间质中分离的DNA显示出进行性降解，这一过程可以通过放线菌素- D或环己亚胺处理和缓冲细胞内钙来阻止。这些结果表明后肾间质具有细胞凋亡的程序性。间质与异源诱导剂、胚胎脊髓的孵育阻止了这种DNA降解。为了研究诱导因子阻止细胞凋亡的机制，我们测试了蛋白激酶C调节剂在这一过程中的作用。佛波酯模拟了诱导剂的作用，而staurosporine（这种蛋白激酶的抑制剂）阻止了诱导剂的作用。EGF也能阻止DNA降解，但不会导致分化。这些结果表明，间充质向上皮细胞的转化至少需要两个步骤：拯救间充质免于凋亡和诱导分化。
During metanephric development, non-polarized mesenchymal cells are induced to form the epithelial structures of the nephron following interaction with extracellular matrix proteins and factors produced by the inducing tissue, ureteric bud. This induction can occur in a transfilter organ culture system where it can also be produced by heterologous cells such as the embryonic spinal cord. We found that when embryonic mesenchyme was induced in vitro and in vivo, many of the cells surrounding the new epithelium showed morphological evidence of programmed cell death (apoptosis) such as condensed nuclei, fragmented cytoplasm, and cell shrinking. A biochemical correlate of apoptosis is the transcriptional activation of a calcium-sensitive endonuclease. Indeed, DNA isolated from uninduced mesenchyme showed progressive degradation, a process that was prevented by treatment with actinomycin- D or cycloheximide and by buffering intracellular calcium. These results demonstrate that the metanephric mesenchyme is programmed for apoptosis. Incubation of mesenchyme with a heterologous inducer, embryonic spinal cord prevented this DNA degradation. To investigate the mechanism by which inducers prevented apoptosis we tested the effects of protein kinase C modulators on this process. Phorbol esters mimicked the effects of the inducer and staurosporine, an inhibitor of this protein kinase, prevented the effect of the inducer. EGF also prevented DNA degradation but did not lead to differentiation. These results demonstrate that conversion of mesenchyme to epithelial requires at least two steps, rescue of the mesenchyme from apoptosis and induction of differentiation.