Frontiers in Cellular Neuroscience (Sep 2013)

Sonic Hedgehog modulates EGFR dependent proliferation of Neural Stem Cells during late mouse embryogenesis through EGFR Transactivation.

  • Veronica Alejandra Palma,
  • Gisela eReinchisi,
  • Gisela eReinchisi,
  • Gisela eReinchisi,
  • Margarita eParada,
  • Margarita eParada,
  • Claudia eOyanadel,
  • Ronan eShaughnessy,
  • Pablo eLois,
  • Alfonso eGonzalez

DOI
https://doi.org/10.3389/fncel.2013.00166
Journal volume & issue
Vol. 7

Abstract

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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 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.

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