%A Palma,Veronica %A Reinchisi,Gisela %A Parada,Margarita %A Oyanadel,Claudia %A Shaughnessy,Ronan %A Lois,Pablo %A Gonzalez,Alfonso %D 2013 %J Frontiers in Cellular Neuroscience %C %F %G English %K Shh,EGFR,radial glial cells,transactivation,proliferation,Cancer,neural progenitors %Q %R 10.3389/fncel.2013.00166 %W %L %M %P %7 %8 2013-September-26 %9 Original Research %+ Dr Veronica Palma,University of Chile,Department of Biology,Las Palmeras 3425, Edificio Milenio,Facultad de Ciencias,U. de Chile,Santiago,7800024,Santiago,Chile,vpalma@uchile.cl %# %! Sonic Hedgehog modulates EGF responsiveness through EGFR transactivation %* %< %T Sonic Hedgehog modulates EGFR dependent proliferation of neural stem cells during late mouse embryogenesis through EGFR transactivation %U https://www.frontiersin.org/articles/10.3389/fncel.2013.00166 %V 7 %0 JOURNAL ARTICLE %@ 1662-5102 %X 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.