Notch signaling inhibits PC12 cell neurite outgrowth via RBP-J-dependent and -independent mechanisms.

The Notch signaling pathway has been implicated in the control of neurite extension, although the mechanisms are unknown. In this report, we studied the role of RBP-J/CBF-1 activation, the primary mediator of Notch signaling, in Notch-mediated regulation of neurite outgrowth in PC12 cells. Expression of constitutively active Notch proteins decreased neurite length and number after NGF treatment. In contrast, an inactive Notch protein had no effect on neurite extension. A dominant negative RBP-J construct prevented the reduction of neurite outgrowth by Notch. Conversely, an activated form of RBP-J decreased neurite length but failed to reduce neurite number. In summary, Notch activation inhibited PC12 cell neurite outgrowth by both RBP-J-dependent and -independent pathways. Copyright 2002 S. Karger AG, Basel