Limits...
The critical role of cyclin D2 in adult neurogenesis.

Kowalczyk A, Filipkowski RK, Rylski M, Wilczynski GM, Konopacki FA, Jaworski J, Ciemerych MA, Sicinski P, Kaczmarek L - J. Cell Biol. (2004)

Bottom Line: In contrast, genetic ablation of cyclin D1 does not affect adult neurogenesis.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Neurobiology, Nencki Institute, 02-093 Warsaw, Poland.

ABSTRACT
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.

Show MeSH

Related in: MedlinePlus

Specificity of the deficit in BrdU incorporation in D2 KO mouse brain. (a) The WT mice displayed significant (P < 0.05), over twofold, increase in the number of BrdU-positive cells in the hippocampal DG after 2 mo of animal exposure to the enriched environment. No significant change was observed in the D2 KO hippocampi. *, P < 0.05. (b and c) Lack of difference in the BrdU-labeled neurons in the olfactory epithelium of the nasal turbinates in WT and D2 KO. (d–i) BrdU incorporation following mechanical injury of the cerebral cortex. BrdU extensive labeling around the site of injury to the cortex in WT (d and f) as well as cyclin D2 KO (e and g) brains. No BrdU labeling in the DG of D2 KO animals (i) observed in WT (h, arrows). DG, dentate gyrus; B.I., brain injury area. Bars: (b and c) 16 μm; (f and g) 500 μm.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2172537&req=5

fig2: Specificity of the deficit in BrdU incorporation in D2 KO mouse brain. (a) The WT mice displayed significant (P < 0.05), over twofold, increase in the number of BrdU-positive cells in the hippocampal DG after 2 mo of animal exposure to the enriched environment. No significant change was observed in the D2 KO hippocampi. *, P < 0.05. (b and c) Lack of difference in the BrdU-labeled neurons in the olfactory epithelium of the nasal turbinates in WT and D2 KO. (d–i) BrdU incorporation following mechanical injury of the cerebral cortex. BrdU extensive labeling around the site of injury to the cortex in WT (d and f) as well as cyclin D2 KO (e and g) brains. No BrdU labeling in the DG of D2 KO animals (i) observed in WT (h, arrows). DG, dentate gyrus; B.I., brain injury area. Bars: (b and c) 16 μm; (f and g) 500 μm.

Mentions: It has been reported that exploration of a novel, enriched environment produces increase in the BrdU labeling in the hippocampus (Rosenzweig and Bennett, 1996; Kempermann et al., 1997; van Praag et al., 2000). We used such a treatment to see whether or not it may induce neurogenesis in the brain of cyclin D2 KO mice. However, no increase in the number of scarce BrdU-positive cells in the hippocampi of the D2 KO animals was observed (Fig. 2 a). In contrast, such a phenomenon was clear in WT mice, with over twofold increase of hippocampal BrdU labeling.


The critical role of cyclin D2 in adult neurogenesis.

Kowalczyk A, Filipkowski RK, Rylski M, Wilczynski GM, Konopacki FA, Jaworski J, Ciemerych MA, Sicinski P, Kaczmarek L - J. Cell Biol. (2004)

Specificity of the deficit in BrdU incorporation in D2 KO mouse brain. (a) The WT mice displayed significant (P < 0.05), over twofold, increase in the number of BrdU-positive cells in the hippocampal DG after 2 mo of animal exposure to the enriched environment. No significant change was observed in the D2 KO hippocampi. *, P < 0.05. (b and c) Lack of difference in the BrdU-labeled neurons in the olfactory epithelium of the nasal turbinates in WT and D2 KO. (d–i) BrdU incorporation following mechanical injury of the cerebral cortex. BrdU extensive labeling around the site of injury to the cortex in WT (d and f) as well as cyclin D2 KO (e and g) brains. No BrdU labeling in the DG of D2 KO animals (i) observed in WT (h, arrows). DG, dentate gyrus; B.I., brain injury area. Bars: (b and c) 16 μm; (f and g) 500 μm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172537&req=5

fig2: Specificity of the deficit in BrdU incorporation in D2 KO mouse brain. (a) The WT mice displayed significant (P < 0.05), over twofold, increase in the number of BrdU-positive cells in the hippocampal DG after 2 mo of animal exposure to the enriched environment. No significant change was observed in the D2 KO hippocampi. *, P < 0.05. (b and c) Lack of difference in the BrdU-labeled neurons in the olfactory epithelium of the nasal turbinates in WT and D2 KO. (d–i) BrdU incorporation following mechanical injury of the cerebral cortex. BrdU extensive labeling around the site of injury to the cortex in WT (d and f) as well as cyclin D2 KO (e and g) brains. No BrdU labeling in the DG of D2 KO animals (i) observed in WT (h, arrows). DG, dentate gyrus; B.I., brain injury area. Bars: (b and c) 16 μm; (f and g) 500 μm.
Mentions: It has been reported that exploration of a novel, enriched environment produces increase in the BrdU labeling in the hippocampus (Rosenzweig and Bennett, 1996; Kempermann et al., 1997; van Praag et al., 2000). We used such a treatment to see whether or not it may induce neurogenesis in the brain of cyclin D2 KO mice. However, no increase in the number of scarce BrdU-positive cells in the hippocampi of the D2 KO animals was observed (Fig. 2 a). In contrast, such a phenomenon was clear in WT mice, with over twofold increase of hippocampal BrdU labeling.

Bottom Line: In contrast, genetic ablation of cyclin D1 does not affect adult neurogenesis.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cellular Neurobiology, Nencki Institute, 02-093 Warsaw, Poland.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus