title: Sonic Hedgehog modulates EGFR dependent proliferation of neural stem cells during late mouse embryogenesis through EGFR transactivation.
abstract: Sonic Hedgehog (Shh/GLI) and EGFR signaling pathways modulate Neural Stem Cell (NSC) proliferation. How these signals cooperate is therefore critical for understanding normal brain development and function. Here we report a novel acute effect of Shh signaling on EGFR function. We show that during late neocortex development, Shh mediates the activation of the ERK1/2 signaling pathway in Radial Glial cells (RGC) through EGFR transactivation. This process is dependent on metalloprotease activity and accounts for almost 50% of the EGFR-dependent mitogenic response of late NSCs. Furthermore, in HeLa cancer cells, a well-known model for studying the EGFR receptor function, Shh also induces cell proliferation involving EGFR activation, as reflected by EGFR internalization and ERK1/2 phosphorylation. These findings may have important implications for understanding the mechanisms that regulate NSC proliferation during neurogenesis and may lead to novel approaches to the treatment of tumors.
authors.affiliation: Centro FONDAP de Regulación del Genoma, Facultad de Ciencias, Universidad de Chile Santiago, Chile ; Departamento de Inmunología Clínica y Reumatología, Departamento de Biología Celular y Molecular, Facultad de Medicina, Facultad de Ciencias Biológicas, Centro de Envejecimiento y Regeneración, Pontificia Universidad Católica de Chile Santiago, Chile.
authors.forename: Gisela
authors.initials: G
authors.lastname: Reinchisi
authors.forename: Margarita
authors.initials: M
authors.lastname: Parada
authors.forename: Pablo
authors.initials: P
authors.lastname: Lois
authors.forename: Claudia
authors.initials: C
authors.lastname: Oyanadel
authors.forename: Ronan
authors.initials: R
authors.lastname: Shaughnessy
authors.forename: Alfonso
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Verónica
authors.initials: V
authors.lastname: Palma
keywords: EGFR; Radial Glial Cells; Shh; cancer; neural progenitors; proliferation; transactivation