Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan; Division of Biological Science, Graduate School of Science, Nagoya University, Nagoya 464-8602, Japan.
Cell Rep. 2013 Nov 27;5(4):926-32. doi: 10.1016/j.celrep.2013.10.021. Epub 2013 Nov 14.
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.
小分子 GTPase Rho 和 mDia2（Rho 调节的肌动蛋白成核因子）是培养细胞胞质分裂的关键调节因子。然而，它们在哺乳动物发育过程中参与胞质分裂的作用仍不清楚。本文通过生成 mDia2 缺失的小鼠，研究 Rho 信号在发育过程中胞质分裂中的作用。mDia2 缺失的小鼠可存活至胚胎第 11.5 天（E11.5），表现出严重的贫血和多核红细胞，并在 E12.5 时死于子宫内。mDia2 缺失的红细胞正常分化，尽管时间延迟，但在晚期从原红细胞向网织红细胞分化过程中，有丝分裂失败，F-肌动蛋白在胞质分裂沟中的积累减少。另一方面，Rho 的失活诱导更早的前体细胞阶段的有丝分裂失败。然而，mDia2 缺失的红细胞能够去核其细胞核。因此，这些发现表明 mDia2 在红细胞生成过程中的体内有丝分裂中具有关键作用，并进一步表明发育过程中的胞质分裂机制在 Rho 下游存在分歧。它们还表明胞质分裂和去核利用不同的机制。
