EGF induces CREB and ERK activation at the wall of the mouse lateral ventricles

The subependymal zone at the lateral ventricular wall represents a major neurogenic niche of the adult mammalian brain and continuously provides new neurons for the olfactory bulb. A mosaic of stem and progenitor cells in this niche has the potential to respond to multiple signals including growth factors such as EGF. Recent studies using long-term ventricular infusion of EGF demonstrate intense cell proliferation around the ventricular wall, implicating the presence of EGF-reactive cells also outside the classical neurogenic lateral niche. Here we show that intraventricular injection of EGF induces within minutes CREB and ERK phosphorylation in astrocyte-like progenitor cells (type B cells) and EGF receptor-expressing transit-amplifying progenitor cells-both in the striatal and septal ventricular walls. EGF infusion for 6 days induced continued CREB and ERK activation in nestin+ cells paralleled by intense periventricular cell proliferation. In addition, the ependyma became EGF receptor-immunoreactive, revealed intense CREB phosphorylation and underwent partial de-differentiation. Our results demonstrate that intraventricular application of EGF induces CREB and ERK phosphorylation along the entire ventricular walls and thus permits a direct identification of EGF-responsive cell types. They further support the notion that not only the striatal ventricular wall where the SEZ is located but also the septal ventricular wall carries latent potential for the formation of neurons and glial cells.