Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis.
Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis.
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DOI：
10.1016/j.celrep.2013.10.021
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发表时间：
2013-11
期刊：
影响因子：
8.8
通讯作者：
Sadanori Watanabe;Tihana De Zan;T. Ishizaki;Shingo Yasuda;H. Kamijo;Daisuke Yamada;T. Aoki;H. Kiyonari;H. Kaneko;R. Shimizu;Masayuki Yamamoto;Gohta Goshima;S. Narumiya
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文献类型：
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作者：
Sadanori Watanabe;Tihana De Zan;T. Ishizaki;Shingo Yasuda;H. Kamijo;Daisuke Yamada;T. Aoki;H. Kiyonari;H. Kaneko;R. Shimizu;Masayuki Yamamoto;Gohta Goshima;S. Narumiya
小的GTdR Rho和mDia 2，一种Rho调节的肌动蛋白成核剂，在培养的细胞中作为胞质分裂的关键调节剂发挥作用。然而，它们在哺乳动物发育过程中参与胞质分裂仍然是未知的。在这里，我们产生了mDia 2缺陷的小鼠，并研究了Rho信号在发育过程中胞质分裂中的作用。mDia 2缺陷型小鼠存活至胚胎第11.5天（E11.5），表现出严重贫血伴多核成红细胞，并在E12.5时在子宫内死亡。mDia 2缺陷型红系细胞分化正常，但以延迟的方式，但表现出胞质分裂失败，在从原成红细胞分化的晚期期间，在卵裂沟中F-肌动蛋白的积累减少。另一方面，Rho的失活诱导早期祖细胞阶段的胞质分裂失败。然而，mDia 2缺陷型成红细胞能够使其细胞核去核。因此，我们的研究结果表明，在红细胞生成过程中，mDia 2在体内胞质分裂中起关键作用，并进一步表明发育中的胞质分裂机制在Rho下游发散。他们还证明胞质分裂和去核利用不同的机制。
The small GTPase Rho and mDia2, a Rho-regulated actin nucleator, function as critical regulators of cytokinesis in cultured cells. However, their involvement in cytokinesis during mammalian development remains unknown. Here, we generated mice deficient in mDia2 and examined the role of Rho signaling in cytokinesis during development. mDia2-deficient mice survive until embryonic day 11.5 (E11.5), exhibit severe anemia with multinucleate erythroblasts, and die in utero by E12.5. mDia2-deficient erythroid cells differentiate normally, though in a delayed manner, but exhibit cytokinesis failure with decreased accumulation of F-actin in the cleavage furrow during late differentiation from proerythroblasts. On the other hand, inactivation of Rho induces cytokinesis failure from the earlier progenitor stage. mDia2-deficient erythroblasts, however, are able to enucleate their nuclei. Our findings have thus revealed that mDia2 functions critically in cytokinesis in vivo during erythropoiesis and further suggest that the cytokinesis mechanism in development diverges downstream of Rho. They also demonstrate that cytokinesis and enucleation utilize different mechanisms.