Neural stem cell interkinetic nuclear migration is controlled by a phosphatidylinositol transfer protein/non-canonical planar cell polarity signaling axis Institutional Repository Document uri icon


  • The mammalian neocortex undergoes explosive expansion during embryonic development. From an evolutionary perspective, higher complexity of the neocortex is accompanied by a prominent expansion in its lateral dimension so that the neocortical surface area is increased. Expansion in the radial dimension throughout evolution is limited so that neocortical thickness is strongly restricted13. The underlying mechanisms for restricting neocortical thickness remain unclear. Expansion of the developing mouse neocortex is driven by neurogenesis which is itself primarily fueled by neural stem cells (NSCs). NSCs form a pseudostratified epithelium and exhibit a hallmark cell cycle-dependent nuclear movement termed interkinetic nuclear migration (IKNM) 24. While IKNM plays a critical role in cell fate determination, it remains a poorly understood process. Herein, we demonstrate IKNM relies on a phosphatidylinositol transfer protein (PITP)-noncanonical planar cell polarity (ncPCP) signaling axis that restricts radial expansion of the developing neocortex. Ablation of PITP/PITP in NSCs compromised IKNM -- resulting in a thickened neocortex and perturbed curvature of its ventricular surface. Those phenotypic derangements in IKNM and neocortical morphogenesis were recapitulated in mouse embryos individually ablated for two ncPCP receptor gene activities and in a mosaic neocortex expressing a dominant-negative variant of a third ncPCP receptor. Finally, PITP signaling links to ncPCP pathway activity by promoting membrane trafficking of a subset of ncPCP receptors from the trans-Golgi network to the NSC cell surface. We conclude IKNM is a driving force for a special form of convergent extension regulated by coupling PITP-mediated phosphoinositide signaling with activity of the evolutionarily conserved ncPCP pathway.

author list (cited authors)

  • Xie, Z., & Bankaitis, V. A.

complete list of authors

  • Xie, Zhigang||Bankaitis, Vytas A

Book Title

  • bioRxiv