Developmental regulation of the effects of fibroblast growth factor‐2 and 1‐octanol on neuronogenesis: Implications for a hypothesis relating to mitogen–antimitogen opposition

Abstract

Neocortical neurons arise from a pseudostratified ventricular epithelium (PVE) that lies within the ventricular zone (VZ) at the margins of the embryonic cerebral ventricles. We examined the effects of fibroblast growth factor‐2 (FGF‐2) and 1‐octanol on cell output behavior of the PVE in explants of the embryonic mouse cerebral wall. FGF‐2 is mitogenic and 1‐octanol antimitogenic in the PVE. Whereas all postmitotic cells migrate out of the VZ in vivo, in the explants some postmitotic cells remain within the VZ. We refer to these cells as the indeterminate or I fraction, because they neither exit from the VZ nor reenter S phase as part of the proliferative (P) fraction. They are considered to be either in an extremely prolonged G₁ phase, unable to pass the G₁/S transition, or in the G₀ state. The I fate choice is modulated by both FGF‐2 and 1‐octanol. FGF‐2 decreased the I fraction and increased the P fraction. In contrast, 1‐octanol increased the I fraction and nearly eliminated the P fraction. The effects of FGF‐2 and 1‐octanol were developmentally regulated, in that they were observed in the developmentally advanced lateral region of the cerebral wall but not in the medial region.