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Regulation of interkinetic nuclear migration by cell cycle-coupled active and passive mechanisms in the developing brain.

Kosodo Y, Suetsugu T, Suda M, Mimori-Kiyosue Y, Toida K, Baba SA, Kimura A, Matsuzaki F - EMBO J. (2011)

Bottom Line: Here, we show that INM proceeds through the cell cycle-dependent linkage of cell-autonomous and non-autonomous mechanisms.In contrast, in vivo observations of implanted microbeads, acute S-phase arrest of surrounding cells and computational modelling suggest that the basal migration of G1-phase nuclei depends on a displacement effect by G2-phase nuclei migrating apically.Our model for INM explains how the dynamics of neural progenitors harmonize their extensive proliferation with the epithelial architecture in the developing brain.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe, Japan. kosodo@med.kawasaki-m.ac.jp

ABSTRACT
A hallmark of neurogenesis in the vertebrate brain is the apical-basal nuclear oscillation in polarized neural progenitor cells. Known as interkinetic nuclear migration (INM), these movements are synchronized with the cell cycle such that nuclei move basally during G1-phase and apically during G2-phase. However, it is unknown how the direction of movement and the cell cycle are tightly coupled. Here, we show that INM proceeds through the cell cycle-dependent linkage of cell-autonomous and non-autonomous mechanisms. During S to G2 progression, the microtubule-associated protein Tpx2 redistributes from the nucleus to the apical process, and promotes nuclear migration during G2-phase by altering microtubule organization. Thus, Tpx2 links cell-cycle progression and autonomous apical nuclear migration. In contrast, in vivo observations of implanted microbeads, acute S-phase arrest of surrounding cells and computational modelling suggest that the basal migration of G1-phase nuclei depends on a displacement effect by G2-phase nuclei migrating apically. Our model for INM explains how the dynamics of neural progenitors harmonize their extensive proliferation with the epithelial architecture in the developing brain.

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Quantitative tracking of nuclear movement of cortical neural progenitor cells in embryonic mouse brain slice cultures. (A) Schematic model of INM of neural progenitor cells. Nuclei in the VZ, the closest tissue layer to the ventral surface of the developing brain, show an oscillatory movement along the apical–basal epithelial axis that is associated with the phase of the cell cycle (see Introduction). The colour code of cell-cycle phases is indicated on the right. (B) Representative movement of a nucleus undergoing INM. Nuclei of neural progenitor cells were labelled by NLS-GFP, and their movements in slice cultures prepared from E13.5 mouse brains were tracked by time-lapse microscopy. Using the tracking software, positions of nuclei from the apical surface (y-coordinate) were measured according to their incubation time (x-coordinate). The time point at which nuclei showed the most apical localization was defined as zero. Phases of the cell cycle, estimated from previous reports, are indicated below (see Results). Numbers and colour codes of nuclei are indicated on the right (a or b after the numbers indicate daughter cells derived from cell division at the apical surface).
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f1: Quantitative tracking of nuclear movement of cortical neural progenitor cells in embryonic mouse brain slice cultures. (A) Schematic model of INM of neural progenitor cells. Nuclei in the VZ, the closest tissue layer to the ventral surface of the developing brain, show an oscillatory movement along the apical–basal epithelial axis that is associated with the phase of the cell cycle (see Introduction). The colour code of cell-cycle phases is indicated on the right. (B) Representative movement of a nucleus undergoing INM. Nuclei of neural progenitor cells were labelled by NLS-GFP, and their movements in slice cultures prepared from E13.5 mouse brains were tracked by time-lapse microscopy. Using the tracking software, positions of nuclei from the apical surface (y-coordinate) were measured according to their incubation time (x-coordinate). The time point at which nuclei showed the most apical localization was defined as zero. Phases of the cell cycle, estimated from previous reports, are indicated below (see Results). Numbers and colour codes of nuclei are indicated on the right (a or b after the numbers indicate daughter cells derived from cell division at the apical surface).

Mentions: Neural progenitor cells in the VZ exhibit interkinetic nuclear migration (INM), in which their nuclei migrate between the apical surface and the basal part of the VZ in synchrony with the cell cycle (see Figure 1A). After mitosis at the apical surface (M-phase), the nuclei migrate basally during G1-phase and subsequently stay at the basal region of the VZ during S-phase. In G2-phase, the nuclei migrate apically, entering M-phase upon reaching the apical surface. This characteristic oscillation of the nuclei of neural progenitor cells was first identified in the embryonic neuroepithelium more than 70 years ago (Sauer, 1935), and was experimentally verified thereafter (Sauer and Walker, 1959; Fujita, 1960). INM has been observed in other epithelial tissues, including chick basilar papilla (Raphael et al, 1994) and embryonic mouse liver buds (Bort et al, 2006), suggesting that this process is a hallmark not only of neuroepithelium, but of all pseudostratified epithelia.


Regulation of interkinetic nuclear migration by cell cycle-coupled active and passive mechanisms in the developing brain.

Kosodo Y, Suetsugu T, Suda M, Mimori-Kiyosue Y, Toida K, Baba SA, Kimura A, Matsuzaki F - EMBO J. (2011)

Quantitative tracking of nuclear movement of cortical neural progenitor cells in embryonic mouse brain slice cultures. (A) Schematic model of INM of neural progenitor cells. Nuclei in the VZ, the closest tissue layer to the ventral surface of the developing brain, show an oscillatory movement along the apical–basal epithelial axis that is associated with the phase of the cell cycle (see Introduction). The colour code of cell-cycle phases is indicated on the right. (B) Representative movement of a nucleus undergoing INM. Nuclei of neural progenitor cells were labelled by NLS-GFP, and their movements in slice cultures prepared from E13.5 mouse brains were tracked by time-lapse microscopy. Using the tracking software, positions of nuclei from the apical surface (y-coordinate) were measured according to their incubation time (x-coordinate). The time point at which nuclei showed the most apical localization was defined as zero. Phases of the cell cycle, estimated from previous reports, are indicated below (see Results). Numbers and colour codes of nuclei are indicated on the right (a or b after the numbers indicate daughter cells derived from cell division at the apical surface).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3101991&req=5

f1: Quantitative tracking of nuclear movement of cortical neural progenitor cells in embryonic mouse brain slice cultures. (A) Schematic model of INM of neural progenitor cells. Nuclei in the VZ, the closest tissue layer to the ventral surface of the developing brain, show an oscillatory movement along the apical–basal epithelial axis that is associated with the phase of the cell cycle (see Introduction). The colour code of cell-cycle phases is indicated on the right. (B) Representative movement of a nucleus undergoing INM. Nuclei of neural progenitor cells were labelled by NLS-GFP, and their movements in slice cultures prepared from E13.5 mouse brains were tracked by time-lapse microscopy. Using the tracking software, positions of nuclei from the apical surface (y-coordinate) were measured according to their incubation time (x-coordinate). The time point at which nuclei showed the most apical localization was defined as zero. Phases of the cell cycle, estimated from previous reports, are indicated below (see Results). Numbers and colour codes of nuclei are indicated on the right (a or b after the numbers indicate daughter cells derived from cell division at the apical surface).
Mentions: Neural progenitor cells in the VZ exhibit interkinetic nuclear migration (INM), in which their nuclei migrate between the apical surface and the basal part of the VZ in synchrony with the cell cycle (see Figure 1A). After mitosis at the apical surface (M-phase), the nuclei migrate basally during G1-phase and subsequently stay at the basal region of the VZ during S-phase. In G2-phase, the nuclei migrate apically, entering M-phase upon reaching the apical surface. This characteristic oscillation of the nuclei of neural progenitor cells was first identified in the embryonic neuroepithelium more than 70 years ago (Sauer, 1935), and was experimentally verified thereafter (Sauer and Walker, 1959; Fujita, 1960). INM has been observed in other epithelial tissues, including chick basilar papilla (Raphael et al, 1994) and embryonic mouse liver buds (Bort et al, 2006), suggesting that this process is a hallmark not only of neuroepithelium, but of all pseudostratified epithelia.

Bottom Line: Here, we show that INM proceeds through the cell cycle-dependent linkage of cell-autonomous and non-autonomous mechanisms.In contrast, in vivo observations of implanted microbeads, acute S-phase arrest of surrounding cells and computational modelling suggest that the basal migration of G1-phase nuclei depends on a displacement effect by G2-phase nuclei migrating apically.Our model for INM explains how the dynamics of neural progenitors harmonize their extensive proliferation with the epithelial architecture in the developing brain.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe, Japan. kosodo@med.kawasaki-m.ac.jp

ABSTRACT
A hallmark of neurogenesis in the vertebrate brain is the apical-basal nuclear oscillation in polarized neural progenitor cells. Known as interkinetic nuclear migration (INM), these movements are synchronized with the cell cycle such that nuclei move basally during G1-phase and apically during G2-phase. However, it is unknown how the direction of movement and the cell cycle are tightly coupled. Here, we show that INM proceeds through the cell cycle-dependent linkage of cell-autonomous and non-autonomous mechanisms. During S to G2 progression, the microtubule-associated protein Tpx2 redistributes from the nucleus to the apical process, and promotes nuclear migration during G2-phase by altering microtubule organization. Thus, Tpx2 links cell-cycle progression and autonomous apical nuclear migration. In contrast, in vivo observations of implanted microbeads, acute S-phase arrest of surrounding cells and computational modelling suggest that the basal migration of G1-phase nuclei depends on a displacement effect by G2-phase nuclei migrating apically. Our model for INM explains how the dynamics of neural progenitors harmonize their extensive proliferation with the epithelial architecture in the developing brain.

Show MeSH
Related in: MedlinePlus