Radial Glial Identity Is Promoted by Notch1 Signaling in the Murine Forebrain

TLDR

Notch signaling is generally known to inhibit neural differentiation in vertebrates. The study aimed to determine whether Notch could also promote specific early cell fates. Activated Notch1 was introduced into the mouse forebrain before neurogenesis using a retroviral vector and ultrasound imaging. NIC activation caused infected cells to become radial glia during embryogenesis and later periventricular astrocytes, indicating that Notch1 promotes radial glial identity and links embryonic radial glia to adult neural stem cells.

Abstract

In vertebrates, Notch signaling is generally thought to inhibit neural differentiation. However, whether Notch can also promote specific early cell fates in this context is unknown. We introduced activated Notch1 (NIC) into the mouse forebrain, before the onset of neurogenesis, using a retroviral vector and ultrasound imaging. During embryogenesis, NIC-infected cells became radial glia, the first specialized cell type evident in the forebrain. Thus, rather than simply inhibiting differentiation, Notch1 signaling promoted the acquisition of an early cellular phenotype. Postnatally, many NIC-infected cells became periventricular astrocytes, cells previously shown to be neural stem cells in the adult. These results suggest that Notch1 promotes radial glial identity during embryogenesis, and that radial glia may be lineally related to stem cells in the adult nervous system.