Cell cycle during neuronal migration and neocortical lamination

Abstract

Objectives: In order to understand the relationships between neocortical lamination and cell cycle, various cells, such as neural stem cell, migrating postmitotic neuron, Cajal-Retzius (CR) cell, and mature pyramidal cell in various cell phases were investigated in mouse cortices.

Methods: With mouse neocortex and hippocampus, the immunofluorescent labeling, BrdU assay, and DiI tracing technique were implemented in the study.

Results: (1) During mouse development, the neocortex expressed different proteins, such as FOXP2, CDP, and Nestin, which could be used as the markers for cortical lamination. (2) The neural stem cells were mainly located in the subventricular zone, with the expressions of Nestin, Cyclin A2, Cyclin E1, and CDT1, suggesting that they were in the repeated cell cycle. Furthermore, the migrating neurons in the neocortex were Cyclin D1- (G1 phase-specific marker) positive, suggesting that they were in the G1 phase. However, Pyramidal cells that developed from postmitotic migrating neurons and settled in the cortical plate were Cyclin D1- negative, suggesting that they were in the G0 phase. (3) Reelin positive CR cells appeared in the molecular layer of the neocortex in early embryonic day (E10), which could express Cyclin A2, Cyclin E1, and CDT1 as pyramidal cells, but not Cyclin D1, suggesting that they may have exited the cell cycle and entered the G0 phase.

Conclusion: The neural migration, neural proliferation, and cell cycle alterations play an important role during cortical lamination. During the cortical development and lamination, the neural stem cells and migrating postmitotic neurons are in different cell cycle phases, but pyramidal cells and CR cells have exited the cell cycle.

Keywords: cell cycle; cortical lamination; neocortex; neuron migration; pyramidal cells.