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Interkinetic nuclear migration generates and opposes ventricular-zone crowding: insight into tissue mechanics.

Miyata T, Okamoto M, Shinoda T, Kawaguchi A - Front Cell Neurosci (2015)

Bottom Line: This review will summarize and discuss several topics: the nature of the INM exhibited by neural progenitor cells, the mechanical difficulties associated with INM in the developing cerebral cortex, the community-level mechanisms underlying collective and efficient INM, the impact on overall brain formation when NE/VZ is overcrowded due to loss of INM, and whether and how neural progenitor INM varies among mammalian species.These discussions will be based on recent findings obtained in live, three-dimensional specimens using quantitative and mechanical approaches.A consideration of the physical aspects in the NE/VZ and the mechanical difficulties associated with high-degree pseudostratification (PS) is important for achieving a better understanding of neocortical development and evolution.

View Article: PubMed Central - PubMed

Affiliation: Anatomy and Cell Biology, Nagoya University Graduate School of Medicine Nagoya, Aichi, Japan.

ABSTRACT
The neuroepithelium (NE) or ventricular zone (VZ), from which multiple types of brain cells arise, is pseudostratified. In the NE/VZ, neural progenitor cells are elongated along the apicobasal axis, and their nuclei assume different apicobasal positions. These nuclei move in a cell cycle-dependent manner, i.e., apicalward during G2 phase and basalward during G1 phase, a process called interkinetic nuclear migration (INM). This review will summarize and discuss several topics: the nature of the INM exhibited by neural progenitor cells, the mechanical difficulties associated with INM in the developing cerebral cortex, the community-level mechanisms underlying collective and efficient INM, the impact on overall brain formation when NE/VZ is overcrowded due to loss of INM, and whether and how neural progenitor INM varies among mammalian species. These discussions will be based on recent findings obtained in live, three-dimensional specimens using quantitative and mechanical approaches. Experiments in which overcrowding was induced in mouse neocortical NE/VZ, as well as comparisons of neocortical INM between mice and ferrets, have revealed that the behavior of NE/VZ cells can be affected by cellular densification. A consideration of the physical aspects in the NE/VZ and the mechanical difficulties associated with high-degree pseudostratification (PS) is important for achieving a better understanding of neocortical development and evolution.

No MeSH data available.


Related in: MedlinePlus

Mechanical tests used for comparing normal and TAG-1–KD cerebral walls (Okamoto et al., 2013). In test 1, a pulse of UV laser was applied on the midpoint of a boundary line formed by two polygonal apices of VZ cells. Vertices at both ends of the laser-targeted side were tracked, and their separation was quantitated. The TAG-1–KD group exhibited greater and more persistent separations. In test 2, bending and curling of slices freshly prepared from normal or TAG-1–KD hemispheres were monitored under a phase-contrast microscope. TAG-1–KD slices that subapically contained many overcrowded (shortened) VZ cells were stiffer, exhibiting no or poorer bending/curling.
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Figure 6: Mechanical tests used for comparing normal and TAG-1–KD cerebral walls (Okamoto et al., 2013). In test 1, a pulse of UV laser was applied on the midpoint of a boundary line formed by two polygonal apices of VZ cells. Vertices at both ends of the laser-targeted side were tracked, and their separation was quantitated. The TAG-1–KD group exhibited greater and more persistent separations. In test 2, bending and curling of slices freshly prepared from normal or TAG-1–KD hemispheres were monitored under a phase-contrast microscope. TAG-1–KD slices that subapically contained many overcrowded (shortened) VZ cells were stiffer, exhibiting no or poorer bending/curling.

Mentions: Monitoring at E12 revealed that the shortened TAG-1–KD VZ cells were overcrowded (subapically about 20% denser than in the normal VZ) (Figure 6, left top corner). Prompted by the hypothesis that VZ cells leave the apical surface when mechanical factors related to cell density increase to an intolerable level, reflecting high-degree proliferation (Smart, 1965, 1972), a series of experiments analyzed the physical condition of the overcrowded TAG-1–KD VZ. Microsurgical techniques such as laser ablation or making slices from hemispheric walls can be used to observe the mechanical conditions of cells or tissues of interest. If a certain portion is under tension or compression in vivo, the incision edges or freed tissue portions will then move according to the original mechanical conditions; these processes can be observed by microscopic monitoring. For example, laser ablation on the apical surface (as in test 1, Figure 6) results in centrifugal movement of the released vertices from the ablation point, revealing that the apical surface is contractile (as a result of the action of actomyosin-dependent mechanisms) and must therefore be under tension. Also, slicing cerebral hemispheric walls allows them to apically bend or curl (test 2, Figure 6). These techniques (destressing or stress-release tests) revealed that the subapical zone of the overcrowded TAG-1–KD VZ was indeed under excessive compression (as revealed in persistent separation of the tracked vertices in test 1 and poorer bending/curling in test 2); this observation was further supported by in silico mechanical simulations (Okamoto et al., 2013). Thus, an overcrowding-induced delamination mechanism, such as the one recently reported in the Drosophila epithelium (Mariani et al., 2012), may also function in the developing mammalian neocortex. Progenitors evacuate (or are forced to exit) from the VZ in response to excessive acute mechanical stress.


Interkinetic nuclear migration generates and opposes ventricular-zone crowding: insight into tissue mechanics.

Miyata T, Okamoto M, Shinoda T, Kawaguchi A - Front Cell Neurosci (2015)

Mechanical tests used for comparing normal and TAG-1–KD cerebral walls (Okamoto et al., 2013). In test 1, a pulse of UV laser was applied on the midpoint of a boundary line formed by two polygonal apices of VZ cells. Vertices at both ends of the laser-targeted side were tracked, and their separation was quantitated. The TAG-1–KD group exhibited greater and more persistent separations. In test 2, bending and curling of slices freshly prepared from normal or TAG-1–KD hemispheres were monitored under a phase-contrast microscope. TAG-1–KD slices that subapically contained many overcrowded (shortened) VZ cells were stiffer, exhibiting no or poorer bending/curling.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4309187&req=5

Figure 6: Mechanical tests used for comparing normal and TAG-1–KD cerebral walls (Okamoto et al., 2013). In test 1, a pulse of UV laser was applied on the midpoint of a boundary line formed by two polygonal apices of VZ cells. Vertices at both ends of the laser-targeted side were tracked, and their separation was quantitated. The TAG-1–KD group exhibited greater and more persistent separations. In test 2, bending and curling of slices freshly prepared from normal or TAG-1–KD hemispheres were monitored under a phase-contrast microscope. TAG-1–KD slices that subapically contained many overcrowded (shortened) VZ cells were stiffer, exhibiting no or poorer bending/curling.
Mentions: Monitoring at E12 revealed that the shortened TAG-1–KD VZ cells were overcrowded (subapically about 20% denser than in the normal VZ) (Figure 6, left top corner). Prompted by the hypothesis that VZ cells leave the apical surface when mechanical factors related to cell density increase to an intolerable level, reflecting high-degree proliferation (Smart, 1965, 1972), a series of experiments analyzed the physical condition of the overcrowded TAG-1–KD VZ. Microsurgical techniques such as laser ablation or making slices from hemispheric walls can be used to observe the mechanical conditions of cells or tissues of interest. If a certain portion is under tension or compression in vivo, the incision edges or freed tissue portions will then move according to the original mechanical conditions; these processes can be observed by microscopic monitoring. For example, laser ablation on the apical surface (as in test 1, Figure 6) results in centrifugal movement of the released vertices from the ablation point, revealing that the apical surface is contractile (as a result of the action of actomyosin-dependent mechanisms) and must therefore be under tension. Also, slicing cerebral hemispheric walls allows them to apically bend or curl (test 2, Figure 6). These techniques (destressing or stress-release tests) revealed that the subapical zone of the overcrowded TAG-1–KD VZ was indeed under excessive compression (as revealed in persistent separation of the tracked vertices in test 1 and poorer bending/curling in test 2); this observation was further supported by in silico mechanical simulations (Okamoto et al., 2013). Thus, an overcrowding-induced delamination mechanism, such as the one recently reported in the Drosophila epithelium (Mariani et al., 2012), may also function in the developing mammalian neocortex. Progenitors evacuate (or are forced to exit) from the VZ in response to excessive acute mechanical stress.

Bottom Line: This review will summarize and discuss several topics: the nature of the INM exhibited by neural progenitor cells, the mechanical difficulties associated with INM in the developing cerebral cortex, the community-level mechanisms underlying collective and efficient INM, the impact on overall brain formation when NE/VZ is overcrowded due to loss of INM, and whether and how neural progenitor INM varies among mammalian species.These discussions will be based on recent findings obtained in live, three-dimensional specimens using quantitative and mechanical approaches.A consideration of the physical aspects in the NE/VZ and the mechanical difficulties associated with high-degree pseudostratification (PS) is important for achieving a better understanding of neocortical development and evolution.

View Article: PubMed Central - PubMed

Affiliation: Anatomy and Cell Biology, Nagoya University Graduate School of Medicine Nagoya, Aichi, Japan.

ABSTRACT
The neuroepithelium (NE) or ventricular zone (VZ), from which multiple types of brain cells arise, is pseudostratified. In the NE/VZ, neural progenitor cells are elongated along the apicobasal axis, and their nuclei assume different apicobasal positions. These nuclei move in a cell cycle-dependent manner, i.e., apicalward during G2 phase and basalward during G1 phase, a process called interkinetic nuclear migration (INM). This review will summarize and discuss several topics: the nature of the INM exhibited by neural progenitor cells, the mechanical difficulties associated with INM in the developing cerebral cortex, the community-level mechanisms underlying collective and efficient INM, the impact on overall brain formation when NE/VZ is overcrowded due to loss of INM, and whether and how neural progenitor INM varies among mammalian species. These discussions will be based on recent findings obtained in live, three-dimensional specimens using quantitative and mechanical approaches. Experiments in which overcrowding was induced in mouse neocortical NE/VZ, as well as comparisons of neocortical INM between mice and ferrets, have revealed that the behavior of NE/VZ cells can be affected by cellular densification. A consideration of the physical aspects in the NE/VZ and the mechanical difficulties associated with high-degree pseudostratification (PS) is important for achieving a better understanding of neocortical development and evolution.

No MeSH data available.


Related in: MedlinePlus