The critical role of cyclin D2 in adult neurogenesis.
Adult neurogenesis (i.e., proliferation and differentiation of neuronal precursors in the adult brain) is responsible for adding new neurons in the dentate gyrus of the hippocampus and in the olfactory bulb. We describe herein that adult mice mutated in the cell cycle regulatory gene Ccnd2, encoding cyclin D2, lack newly born neurons in both of these brain structures. In contrast, genetic ablation of cyclin D1 does not affect adult neurogenesis. Furthermore, we show that cyclin D2 is the only D-type cyclin (out of D1, D2, and D3) expressed in dividing cells derived from neuronal precursors present in the adult hippocampus. In contrast, all three cyclin D mRNAs are present in the cultures derived from 5-day-old hippocampi, when developmental neurogenesis in the dentate gyrus takes place. Thus, our results reveal the existence of molecular mechanisms discriminating adult versus developmental neurogeneses.
Kowalczyk
Anna
A
Department of Molecular and Cellular Neurobiology, Nencki Institute, 02-093 Warsaw, Poland.
Filipkowski
Robert K
RK
Rylski
Marcin
M
Wilczynski
Grzegorz M
GM
Konopacki
Filip A
FA
Jaworski
Jacek
J
Ciemerych
Maria A
MA
Sicinski
Piotr
P
Kaczmarek
Leszek
L
D000818:Animals; D001921:Brain / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000494:pharmacology; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000378:metabolism; D056742:Cyclin D2; D016213:Cyclins / Q000378:metabolism / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D012333:RNA, Messenger; D019938:Cyclin D1; D012313:RNA; D001973:Bromodeoxyuridine