Rac is involved in the interkinetic nuclear migration of cortical progenitor cells.
The small GTPase Rac regulates neuronal behavior, but whether it also functions in neural progenitor cells has not yet been explored. Here we report that Rac contributes to the regulation of nuclear migration in neocortical progenitor cells. Rac1 is expressed by progenitor cells in a unique spatiotemporal pattern. Cross-sectional immunohistochemical examination revealed intense Rac1 immunoreactivity at the ventricular surface. Similar staining patterns were obtained by immunofluorescence for a Rac-activator, Tiam1, and by reactions to detect the GTP-bound (active) form of Rac. En face inspection of the ventricular surface revealed that apical Rac1 localization was most frequent in M-phase cells, and the endfeet of cells in other cell cycle phases also showed apical Rac1 distribution at lower frequencies. To ask whether progenitor cell behavior prior to and during M phase is Rac-dependent, we monitored individual DiI-labeled progenitor cells live in the presence of a Rac inhibitor, NSC23766. We observed significantly retarded adventricular nuclear migration, as well as cytokinesis failures. Similar inhibitory effects were obtained by forced expression of a dominant-negative Rac1. These results suggest that Rac may play a role in interkinetic nuclear migration in the developing mouse brain.
Department of Anatomy and Cell Biology, Nagoya University Graduate School of Medicine, Aichi, Japan.
Sayaka
S
Minobe
Akira
A
Sakakibara
Tomoko
T
Ohdachi
Rieko
R
Kanda
Miyako
M
Kimura
Sayaka
S
Nakatani
Ryosuke
R
Tadokoro
Wataru
W
Ochiai
Yuji
Y
Nishizawa
Akira
A
Mizoguchi
Takeshi
T
Kawauchi
Takaki
T
Miyata
D000367:Age Factors; D000596:Amino Acids / Q000378:metabolism; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D002552:Cerebral Ventricles / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D018274:Electroporation / Q000379:methods; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D055495:Neurogenesis / Q000187:drug effects / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D011247:Pregnancy; D021381:Protein Transport / Q000187:drug effects / Q000235:genetics; D011743:Pyrimidines / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000502:physiology*
D000596:Amino Acids; D000634:Aminoquinolines; D020662:Guanine Nucleotide Exchange Factors; C487513:NSC 23766; D011743:Pyrimidines; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C513260:Tiam1 protein, mouse; D014746:Vimentin; C098463:dolaisoleucine; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D020830:rac1 GTP-Binding Protein