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.

Ethanol inhibition of undifferentiated rat neural progenitor cell replication can be prevented by chlorogenic acid via the NFATc4/CSE signaling pathway

“…The Tbr2‐positive basal progenitors are neuron‐committed progenitors. In addition to the well‐documented controlling role of cyclin D1 on cell replication, it also functions to mediate cell migration and adhesion, events which are disrupted by EtOH (Camarillo & Miranda, 2007; Goodlett & Horn, 2001; Lange et al, 2009; Wu et al, 2021). These functions, neuroblast replication/neuron formation, migration, and adhesion are individually vital elements governing brain development, and if disrupted in combo by ETOH, would clearly be expected to have a highly multifactorial and temporally variable setting yielding neurodevelopmental defects.…”

The impact of maternal immune activation on embryonic brain development

“…The proliferation and migration of neurons is instrumental in defining complex structures within the brain, one of which, the neocortex, is characterized by the lamination of neurons into six distinct layers ( Kostović and Judaš, 2007 ; Guarnieri et al, 2019 ; Wu et al, 2021 ). During early murine cortical development (around E10.5), the first wave of neuronal migration from the VZ and SVZ forms the thin, preplate layer which later splits into the superficial marginal zone and the inner subplate, allowing the cortical plate to form in between ( Figure 1 ).…”

Characterizing the diversity of L2/3 human neocortical neurons in epilepsy

“…This has all been linked to initiation and development for seizure activity (Blumcke et al, 2011, Liang et al, 2020) 18,19 s. In addition to FCD and all of its subtypes, the MCD class of epilepsy also encompasses Tuberous Sclerosis (TSC), hemimegaloencephaly or schizencephaly (Curatolo et al, 2018) 20 . For most of the MCD epilepsies, especially FCD and TSC, the mammalian target of rapamycin (mTOR) pathway which drives the epileptogenesis which is triggers by genetic mutations along the pathway as well as other acquired factors (Cepeda et al, 2012, Curatolo et al, 2018 16,[20][21][22][23][24][25][26][27][28][29][30] .…”