Loss of Cdk2 and Cdk4 induces a switch from proliferation to differentiation in neural stem cells
Lim, Shuhui and Kaldis, Philipp LU
(2012)
In Stem Cells
30(7).
p.1509-1520
- Abstract
During neurogenesis, cell cycle regulators play a pivotal role in ensuring proper proliferation, cell cycle exit, and differentiation of neural precursors. However, the precise role of cyclin-dependent kinases (Cdks) in these processes is not well understood. We generated Cdk2 and Cdk4 double knockout (DKO) mice and found a striking ablation of the intermediate zone and cortical plate in mouse embryonic brain. When neural stem cells (NSCs) were isolated and analyzed, DKO NSCs proliferated comparable to wild type as Cdk1 now binds to cyclin D1 and E1 and assumes the role vacated by the loss of Cdk2 and Cdk4 in phosphorylating Rb. Although compensation was sufficient for the maintenance of selfrenewal and multilineage potential, DKO NSCs... (More)
During neurogenesis, cell cycle regulators play a pivotal role in ensuring proper proliferation, cell cycle exit, and differentiation of neural precursors. However, the precise role of cyclin-dependent kinases (Cdks) in these processes is not well understood. We generated Cdk2 and Cdk4 double knockout (DKO) mice and found a striking ablation of the intermediate zone and cortical plate in mouse embryonic brain. When neural stem cells (NSCs) were isolated and analyzed, DKO NSCs proliferated comparable to wild type as Cdk1 now binds to cyclin D1 and E1 and assumes the role vacated by the loss of Cdk2 and Cdk4 in phosphorylating Rb. Although compensation was sufficient for the maintenance of selfrenewal and multilineage potential, DKO NSCs displayed an altered cell cycle profile and were more prone to neuronal differentiation. This was manifested in vivo as a marked reduction in S-phase length and an increased tendency for neurogenic divisions that prevented proper expansion of the basal progenitor pool. Our data thus demonstrate the induction of neurogenic divisions in the absence of critical mediators of G1/S transition - Cdk2 and Cdk4, and highlight their evolutionary importance in the determination of cortical thickness.
(Less)
- author
- Lim, Shuhui
and Kaldis, Philipp
LU
- publishing date
- 2012-07-01
- type
- Contribution to journal
- publication status
- published
- keywords
- Cells cycle regulation, Cyclin, Cyclin-dependent kinase, Differentiation, Mouse models, Neural stem cells
- in
- Stem Cells
- volume
- 30
- issue
- 7
- pages
- 1509 - 1520
- publisher
- Oxford University Press
- external identifiers
-
- scopus:84862836329
- pmid:22532528
- ISSN
- 1066-5099
- DOI
- 10.1002/stem.1114
- language
- English
- LU publication?
- no
- id
- dcc19fe0-7cf0-40c3-9dd0-cd7c2612fae1
- date added to LUP
- 2019-09-18 13:58:38
- date last changed
- 2024-06-27 05:53:50
@article{dcc19fe0-7cf0-40c3-9dd0-cd7c2612fae1,
abstract = {{<p>During neurogenesis, cell cycle regulators play a pivotal role in ensuring proper proliferation, cell cycle exit, and differentiation of neural precursors. However, the precise role of cyclin-dependent kinases (Cdks) in these processes is not well understood. We generated Cdk2 and Cdk4 double knockout (DKO) mice and found a striking ablation of the intermediate zone and cortical plate in mouse embryonic brain. When neural stem cells (NSCs) were isolated and analyzed, DKO NSCs proliferated comparable to wild type as Cdk1 now binds to cyclin D1 and E1 and assumes the role vacated by the loss of Cdk2 and Cdk4 in phosphorylating Rb. Although compensation was sufficient for the maintenance of selfrenewal and multilineage potential, DKO NSCs displayed an altered cell cycle profile and were more prone to neuronal differentiation. This was manifested in vivo as a marked reduction in S-phase length and an increased tendency for neurogenic divisions that prevented proper expansion of the basal progenitor pool. Our data thus demonstrate the induction of neurogenic divisions in the absence of critical mediators of G1/S transition - Cdk2 and Cdk4, and highlight their evolutionary importance in the determination of cortical thickness.</p>}},
author = {{Lim, Shuhui and Kaldis, Philipp}},
issn = {{1066-5099}},
keywords = {{Cells cycle regulation; Cyclin; Cyclin-dependent kinase; Differentiation; Mouse models; Neural stem cells}},
language = {{eng}},
month = {{07}},
number = {{7}},
pages = {{1509--1520}},
publisher = {{Oxford University Press}},
series = {{Stem Cells}},
title = {{Loss of Cdk2 and Cdk4 induces a switch from proliferation to differentiation in neural stem cells}},
url = {{http://dx.doi.org/10.1002/stem.1114}},
doi = {{10.1002/stem.1114}},
volume = {{30}},
year = {{2012}},
}