Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis.
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.
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.
Sadanori
S
Watanabe
Tihana
T
De Zan
Toshimasa
T
Ishizaki
Shingo
S
Yasuda
Hiroshi
H
Kamijo
Daisuke
D
Yamada
Tomohiro
T
Aoki
Hiroshi
H
Kiyonari
Hiroshi
H
Kaneko
Ritsuko
R
Shimizu
Masayuki
M
Yamamoto
Gohta
G
Goshima
Shuh
S
Narumiya
D000199:Actins; D000818:Animals; D002467:Cell Nucleus; D002478:Cells, Cultured; D048749:Cytokinesis / Q000235:genetics* / Q000502:physiology; D004622:Embryo, Mammalian / Q000502:physiology*; D004900:Erythroblasts / Q000166:cytology; D004920:Erythropoiesis / Q000235:genetics*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009252:NADPH Dehydrogenase / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D020741:rho GTP-Binding Proteins / Q000235:genetics*
D000199:Actins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C508552:Dia2 protein, mouse; D009252:NADPH Dehydrogenase; D020741:rho GTP-Binding Proteins