Differentiating cells mechanically limit the interkinetic nuclear migration of progenitor cells to secure apical cytogenesis.

Many proliferative epithelia are pseudostratified because of cell cycle-dependent interkinetic nuclear migration (IKNM, basal during G1 and apical during G2). Although most epithelia, including early embryonic neuroepithelia (≤100 µm thick), undergo IKNM over the entire apicobasal extent, more apicobasally elongated (300 µm) neural progenitor cells (radial glial cells) in the mid-embryonic mouse cerebral wall move their nuclei only within its apical (100 µm) compartment, leaving the remaining basal region nucleus-free (fiber-like). How this IKNM range [i.e. the thickness of a pseudostratified ventricular zone (VZ)] is determined remains unknown. Here, we report external fencing of IKNM and the VZ by differentiating cells. When a tight stack of multipolar cells immediately basal to the VZ was 'drilled' via acute neuron-directed expression of diphtheria toxin, IKNM of apicobasally connected progenitor cells continued further towards the basal region of the cell (200 µm). The unfencing-induced basally overshot nuclei stay in S phase for too long and do not move apically, suggesting that external limitation of IKNM is necessary for progenitors to undergo normal cytogenetic behaviors. Thus, physical collaboration between progenitors and differentiating cells, including neurons, underlies brain development.