The CDC25B phosphatase shortens the G2 phase of neural progenitors and promotes efficient neuron production.
During embryonic development, changes in cell cycle kinetics have been associated with neurogenesis. This observation suggests that specific cell cycle regulators may be recruited to modify cell cycle dynamics and influence the decision between proliferation and differentiation. In the present study, we investigate the role of core positive cell cycle regulators, the CDC25 phosphatases, in this process. We report that, in the developing chicken spinal cord, only CDC25A is expressed in domains where neural progenitors undergo proliferative self-renewing divisions, whereas the combinatorial expression of CDC25A and CDC25B correlates remarkably well with areas where neurogenesis occurs. We also establish that neural progenitors expressing both CDC25A and CDC25B have a shorter G2 phase than those expressing CDC25A alone. We examine the functional relevance of these correlations using an RNAi-based method that allows us to knock down CDC25B efficiently and specifically. Reducing CDC25B expression results in a specific lengthening of the G2 phase, whereas the S-phase length and the total cell cycle time are not significantly modified. This modification of cell cycle kinetics is associated with a reduction in neuron production that is due to the altered conversion of proliferating neural progenitor cells to post-mitotic neurons. Thus, expression of CDC25B in neural progenitors has two functions: to change cell cycle kinetics and in particular G2-phase length and also to promote neuron production, identifying new roles for this phosphatase during neurogenesis.
Université de Toulouse, CBD, 118 route de Narbonne, F-31062 Toulouse, France.
Emilie
E
Peco
Timothé
T
Escude
Eric
E
Agius
Virginie
V
Sabado
François
F
Medevielle
Bernard
B
Ducommun
Fabienne
F
Pituello
D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D002642:Chick Embryo; D016195:G2 Phase; D009420:Nervous System / Q000196:embryology*; D058953:Neural Stem Cells / Q000166:cytology* / Q000502:physiology; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology*; D020687:cdc25 Phosphatases / Q000096:biosynthesis / Q000378:metabolism*
D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D020687:cdc25 Phosphatases