Interkinetic nuclear migration generates and opposes ventricular-zone crowding: insight into tissue mechanics

Abstract

The neuroepithelium (NE) or ventricular zone (VZ), from which multiple types of brain cells arise, is pseudostratified. In the NE/VZ, neural progenitor cells are elongated along the apicobasal axis, and their nuclei assume different apicobasal positions. These nuclei move in a cell cycle–dependent manner, i.e., apicalward during G2 phase and basalward during G1 phase, a process called interkinetic nuclear migration (INM). This review will summarize and discuss several topics: the nature of the INM exhibited by neural progenitor cells, the mechanical difficulties associated with INM in the developing cerebral cortex, the community-level mechanisms underlying collective and efficient INM, the impact on overall brain formation when NE/VZ is overcrowded due to loss of INM, and whether and how neural progenitor INM varies among mammalian species. These discussions will be based on recent findings obtained in live, three-dimensional specimens using quantitative and mechanical approaches. Experiments in which overcrowding was induced in mouse neocortical NE/VZ, as well as comparisons of neocortical INM between mice and ferrets, have revealed that the behavior of NE/VZ cells can be affected by cellular densification. A consideration of the physical aspects in the NE/VZ and the mechanical difficulties associated with high-degree pseudostratification (PS) is important for achieving a better understanding of neocortical development and evolution.

An On‐Chip Method for Long‐Term Growth and Real‐Time Imaging of Brain Organoids

“…Markers of forebrain neuronal progenitors (FOXG1, PAX6, EMX2, and LHX2) and neurons (NEUN, DCX) should increase over time (Karzbrun et al, 2018). Radial glial cells should exhibit elongated morphology and interkinetic nuclear motion with divisions at the apical surface (Miyata et al, 2014).…”

Interkinetic nuclear migration in the mouse embryonic ureteric epithelium: Possible implication for congenital anomalies of the kidney and urinary tract

“…Interkinetic nuclear migration has been extensively studied in the neural epithelium and other epithelia of ectoderm origin using various methods, including the recently advanced direct time‐lapse video imaging (for review, see Miyata ; Taverna and Huttner ; Willardsen and Link ; Spear and Erickson ; Kosodo ; Miyata et al ). On the other hand, INM‐like nuclear localization shift as well as apical‐limited localization of mitotic figures have long been observed in many other epithelia, not only of endoderm and mesoderm origin in vertebrates, but also in epithelia of invertebrates (for review, see Spear and Erickson ; Lee and Norden ).…”

Differences in the Mechanical Properties of the Developing Cerebral Cortical Proliferative Zone between Mice and Ferrets at both the Tissue and Single-Cell Levels

“…This finding suggests that proliferative cells may sense and respond to excessive mechanical stress generated in the subapical space. It also raises the possibility that similar sensing and responses to mechanical factors might also occur under physiological (non-overcrowded) conditions, possibly coordinating heterogeneous nuclear and somal movements (Miyata et al, 2015; Strzyz et al, 2016). We chose to focus on a microzone near (~10 μm from) the apical surface, where multiple mechanical events, such as mitosis, resultant duplication of nuclear and somal flow, as well as apical constriction, take place.…”