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.

Environmental enrichment rescues memory in mice deficient for the polysialytransferase ST8SiaIV.

The neural cell adhesion molecule NCAM and its association with the polysialic acid (PSA) are believed to contribute to brain structural plasticity that underlies memory formation. Indeed, the attachment of long chains of PSA to the glycoprotein NCAM down-regulates its adhesive properties by altering cell-cell interactions. In the brain, the biosynthesis of PSA is catalyzed by two polysialyltransferases, which are differentially regulated during lifespan. One of them, ST8SiaIV (PST), is predominantly expressed during adulthood whereas the other one, ST8SiaII (STX), dominates during embryonic and post-natal development. To understand the role played by ST8SiaIV during learning and memory and its underlying hippocampal plasticity, we used knockout mice deleted for the enzyme ST8SiaIV (PST-ko mice). At adult age, PST-ko mice show a drastic reduction of PSA-NCAM expression in the hippocampus and intact hippocampal adult neurogenesis. We found that these mice display impaired long-term but not short-term memory in both, spatial and non-spatial behavioral tasks. Remarkably, memory deficits of PST-ko mice were abolished by exposure to environmental enrichment that was also associated with an increased number of PSA-NCAM expressing new neurons in the dentate gyrus of these mice. Whether the presence of a larger pool of immature, likely plastic, new neurons favored the rescue of long-term memory in PST-ko mice remains to be determined. Our findings add new evidence to the role played by PSA in memory consolidation. They also suggest that PSA synthesized by PST critically controls the tempo of new neurons maturation in the adult hippocampus.