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* Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Tsukuba, Ibaraki 305, Japan; and Megakaryocytes undergo a unique differentiation program, becoming polyploid through repeated
cycles of DNA synthesis without concomitant cell division. However, the mechanism underlying this polyploidization remains totally unknown. It has been postulated that polyploidization is due to a skipping of
mitosis after each round of DNA replication. We carried out immunohistochemical studies on mouse bone
marrow megakaryocytes during thrombopoietin-
induced polyploidization and found that during this
process megakaryocytes indeed enter mitosis and
progress through normal prophase, prometaphase, metaphase, and up to anaphase A, but not to anaphase
B, telophase, or cytokinesis. It was clearly observed
that multiple spindle poles were formed as the polyploid megakaryocytes entered mitosis; the nuclear
membrane broke down during prophase; the sister
chromatids were aligned on a multifaced plate, and the
centrosomes were symmetrically located on either side
of each face of the plate at metaphase; and a set of sister chromatids moved into the multiple centrosomes during anaphase A. We further noted that the pair of
spindle poles in anaphase were located in close proximity to each other, probably because of the lack of outward movement of spindle poles during anaphase B. Thus, the reassembling nuclear envelope may enclose all the sister chromatids in a single nucleus at anaphase
and then skip telophase and cytokinesis. These observations clearly indicate that polyploidization of megakaryocytes is not simply due to a skipping of mitosis,
and that the megakaryocytes must have a unique regulatory mechanism in anaphase, e.g., factors regulating
anaphase such as microtubule motor proteins might be involved in this polyploidization process.
Department of Dermatology, Nagoya University School of Medicine Showa-ku, Nagoya 466, Japan
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