Differentiating cells mechanically limit progenitor cells’ interkinetic nuclear migration to secure apical cytogenesis

Many proliferative epithelia are pseudostratified due to 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 (also called “radial glia”) in the mid-embryonic mouse cerebral wall move their nuclei only within its apical (100 µm) compartment, leaving the remaining basal part 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 VZ by differentiating cells. When a tight stack of multipolar cells just basal to VZ was “drilled” via acute neuron-directed expression of diphtheria toxin, IKNM of apicobasally connected progenitor cells continued far basally (200 µm). The unfencing-induced, basally overshot nuclei stay in S phase 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.