A novel function for Foxm1 in interkinetic nuclear migration in the developing telencephalon and anxiety-related behavior.
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.
Key Laboratory of Developmental Genes and Human Diseases, Ministry of Education, Department of Anatomy and Neuroscience, Medical School, Southeast University, Nanjing, 210009, China.
Xiaojing
X
Wu
Xiaochun
X
Gu
Xiaoning
X
Han
Ailing
A
Du
Yan
Y
Jiang
Xiaoyun
X
Zhang
Yanjie
Y
Wang
Guangliang
G
Cao
Chunjie
C
Zhao
D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007700:Kinetics; D051379:Mice; D008817:Mice, Mutant Strains; D055495:Neurogenesis / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D013687:Telencephalon / Q000502:physiology*
D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; C491524:Foxm1 protein, mouse
Foxm1; INM; anxiety-related behavior; cell cycle; neurogenesis