Cell cycle progression is required for nuclear migration of neural progenitor cells.
In the developing brain, neural progenitor cells in the ventricular zone (VZ) show a typical migration pattern-interkinetic nuclear migration, in which nuclear position within the VZ is correlated with the cell cycle. However, the mechanisms underlying this regulation remain unclear. To clarify whether the cell cycle progression controls nuclear migration of neural progenitor cells, we determined whether chemically induced cell cycle arrest affected nuclear migration patterns in the VZ. Administration of 5-azacytidine (5AzC) or cyclophosphamide (CP) to pregnant mice induced cell cycle arrest in the fetal neural progenitor cells of the telencephalon: 5AzC induced G2/M-phase arrest, and CP induced S-phase arrest. We used 5-bromo-2'-deoxyuridine (BrdU) labeling to determine the position of the cell in the cell cycle and the nuclei within the VZ at the same time. Cells arrested in G2/M-phase stopped migrating in the inner area of the VZ. Cells arrested in S-phase stopped migrating in the outer area. These results indicate that nuclear position within the VZ was correlated with cell cycle phase, even when the cell cycle was disrupted, and that the nuclei of neural progenitor cells can migrate only when their cell cycle is going. Our results suggest that cell cycle regulators might control the machinery of migration through a common regulatory mechanism.
Ueno
Masaki
M
Department of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan. ms-ueno@umin.ac.jp
Katayama
Kei-ichi
K
Yamauchi
Hirofumi
H
Nakayama
Hiroyuki
H
Doi
Kunio
K
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001374:Azacitidine / Q000494:pharmacology; D001973:Bromodeoxyuridine / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000502:physiology*; D003520:Cyclophosphamide / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D007150:Immunohistochemistry / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020287:In Situ Nick-End Labeling / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D011247:Pregnancy; D013234:Stem Cells / Q000502:physiology*; D013687:Telencephalon / Q000166:cytology / Q000196:embryology; D013997:Time Factors
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D001973:Bromodeoxyuridine; D001374:Azacitidine