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Thrombopoietin-induced polyploidization of bone marrow megakaryocytes is due to a unique regulatory mechanism in late mitosis.

Nagata Y, Muro Y, Todokoro K - J. Cell Biol. (1997)

Bottom Line: It has been postulated that polyploidization is due to a skipping of mitosis after each round of DNA replication.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.

View Article: PubMed Central - PubMed

Affiliation: Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Tsukuba, Ibaraki 305, Japan.

ABSTRACT
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.

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Schematic drawing of hypothetical mechanism of TPO-induced polyploidization of megakaryocytes. Upper panel shows  a normal mitosis, and lower panel shows the mitosis of megakaryocytes during polyploidization.
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Figure 5: Schematic drawing of hypothetical mechanism of TPO-induced polyploidization of megakaryocytes. Upper panel shows a normal mitosis, and lower panel shows the mitosis of megakaryocytes during polyploidization.

Mentions: Taken together, a model of the polyploidization process of megakaryocytes is shown in Fig. 5. Here, we describe a megakaryocyte polyploidizing from 4N to 8N as an example (lower panel). Two centrosomes duplicate to form four centrosomes in a cell, and the cell normally enters the first step of mitosis, prophase. The chromatin condenses into chromosomes, and the mitotic spindles are formed. The nuclear envelope is normally disrupted, and mitotic spindles enter the nucleus at prometaphase. At metaphase, two planes of the aligned chromosomes cross at right angles, and four pairs of spindle poles are beautifully aligned between the crossed chromosomes. In anaphase, the sets of sister chromatids separate each other and move toward each pole. However, the pair of spindle poles in this stage is located at a closer distance than normal cells (Fig. 5, upper panel), and the pair of spindle poles stay fixed and do not move farther apart as normal cells do. The reassembling nuclear envelope encloses all the sister chromatids into one nucleus because of the lack of outward movement of the spindle poles during anaphase. Without telophase or cytokinesis, the cell with ploidy 8N goes into another round of cell cycle.


Thrombopoietin-induced polyploidization of bone marrow megakaryocytes is due to a unique regulatory mechanism in late mitosis.

Nagata Y, Muro Y, Todokoro K - J. Cell Biol. (1997)

Schematic drawing of hypothetical mechanism of TPO-induced polyploidization of megakaryocytes. Upper panel shows  a normal mitosis, and lower panel shows the mitosis of megakaryocytes during polyploidization.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139799&req=5

Figure 5: Schematic drawing of hypothetical mechanism of TPO-induced polyploidization of megakaryocytes. Upper panel shows a normal mitosis, and lower panel shows the mitosis of megakaryocytes during polyploidization.
Mentions: Taken together, a model of the polyploidization process of megakaryocytes is shown in Fig. 5. Here, we describe a megakaryocyte polyploidizing from 4N to 8N as an example (lower panel). Two centrosomes duplicate to form four centrosomes in a cell, and the cell normally enters the first step of mitosis, prophase. The chromatin condenses into chromosomes, and the mitotic spindles are formed. The nuclear envelope is normally disrupted, and mitotic spindles enter the nucleus at prometaphase. At metaphase, two planes of the aligned chromosomes cross at right angles, and four pairs of spindle poles are beautifully aligned between the crossed chromosomes. In anaphase, the sets of sister chromatids separate each other and move toward each pole. However, the pair of spindle poles in this stage is located at a closer distance than normal cells (Fig. 5, upper panel), and the pair of spindle poles stay fixed and do not move farther apart as normal cells do. The reassembling nuclear envelope encloses all the sister chromatids into one nucleus because of the lack of outward movement of the spindle poles during anaphase. Without telophase or cytokinesis, the cell with ploidy 8N goes into another round of cell cycle.

Bottom Line: It has been postulated that polyploidization is due to a skipping of mitosis after each round of DNA replication.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.

View Article: PubMed Central - PubMed

Affiliation: Tsukuba Life Science Center, The Institute of Physical and Chemical Research (RIKEN), Tsukuba, Ibaraki 305, Japan.

ABSTRACT
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.

Show MeSH