Journal
JOURNAL OF NEUROSCIENCE
Volume 34, Issue 4, Pages 1510-1522Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2549-13.2014
Keywords
anxiety-related behavior; cell cycle; Foxm1; INM; neurogenesis
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Funding
- National Natural Science Foundation of China [91232301, 31171040, 81070904, 31200823]
- National High Technology Research and Development Program of China [2012AA022402]
- National Basic Research Program of China [2013CB733801]
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Interkinetic nuclear migration (INM) is a key feature of cortical neurogenesis. INM functions to maximize the output of the neuroepithelium, and more importantly, balance the self-renewal and differentiation of the progenitors. Although INM has been reported to be highly correlated with the cell cycle, little is known about the effects of cell cycle regulators on INM. In this study, by crossing Foxm1(fl/fl) mice with Emx1-Cre line, we report that a conditional disruption of forkhead transcription factor M1 (Foxm1) in dorsal telencephalon results in abnormal cell cycle progression, leading to impaired INM through the downregulation of Cyclin b1 and Cdc25b. The impairment of INM disturbs the synchronization of apical progenitors (APs) and promotes the transition from APs to basal progenitors (BPs) in a cell-autonomous fashion. Moreover, ablation of Foxm1 causes anxiety-related behaviors in adulthood. Thus, this study provides evidence of linkages among the cell cycle regulator Foxm1, INM, and adult behavior.
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