Loss of a Rho-regulated actin nucleator, mDia2, impairs cytokinesis during mouse fetal erythropoiesis

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins
  • Animals
  • Cell Nucleus
  • Cells, Cultured
  • Cytokinesis / genetics*
  • Cytokinesis / physiology
  • Embryo, Mammalian / physiology*
  • Erythroblasts / cytology
  • Erythropoiesis / genetics*
  • Humans
  • Mice
  • Mice, Knockout
  • Microtubule-Associated Proteins / genetics*
  • NADPH Dehydrogenase / genetics*
  • RNA Interference
  • RNA, Small Interfering
  • rho GTP-Binding Proteins / genetics*


  • Actins
  • Microtubule-Associated Proteins
  • RNA, Small Interfering
  • Dia2 protein, mouse
  • NADPH Dehydrogenase
  • rho GTP-Binding Proteins