Visualizing spatiotemporal dynamics of multicellular cell-cycle progression.
The cell-cycle transition from G1 to S phase has been difficult to visualize. We have harnessed antiphase oscillating proteins that mark cell-cycle transitions in order to develop genetically encoded fluorescent probes for this purpose. These probes effectively label individual G1 phase nuclei red and those in S/G2/M phases green. We were able to generate cultured cells and transgenic mice constitutively expressing the cell-cycle probes, in which every cell nucleus exhibits either red or green fluorescence. We performed time-lapse imaging to explore the spatiotemporal patterns of cell-cycle dynamics during the epithelial-mesenchymal transition of cultured cells, the migration and differentiation of neural progenitors in brain slices, and the development of tumors across blood vessels in live mice. These mice and cell lines will serve as model systems permitting unprecedented spatial and temporal resolution to help us better understand how the cell cycle is coordinated with various biological events.
Sakaue-Sawano
Asako
A
Laboratory for Cell Function and Dynamics, Advanced Technology Development Group, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama 351-0198, Japan.
Kurokawa
Hiroshi
H
Morimura
Toshifumi
T
Hanyu
Aki
A
Hama
Hiroshi
H
Osawa
Hatsuki
H
Kashiwagi
Saori
S
Fukami
Kiyoko
K
Miyata
Takaki
T
Miyoshi
Hiroyuki
H
Imamura
Takeshi
T
Ogawa
Masaharu
M
Masai
Hisao
H
Miyawaki
Atsushi
A
D000818:Animals; D019556:COS Cells; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003584:Cytological Techniques; D005453:Fluorescence; D064248:Geminin; D006367:HeLa Cells; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009024:Morphogenesis; D009369:Neoplasms / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination
C467199:CDT1 protein, human; D018797:Cell Cycle Proteins; C577995:GMNN protein, human; D064248:Geminin; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins