Extracellular signal-regulated protein kinase signaling is uncoupled from initial differentiation of central nervous system stem cells to neurons

Mol Cancer Res. 2002 Dec;1(2):147-54.

Abstract

Knowledge about signaling pathways in response to external signals is needed to understand the regulation of stem cell proliferation and differentiation toward particular cell fates. The Ras/extracellular signal-regulated kinase (ERK) pathway has been suggested to play an essential role in neuronal differentiation. We have examined ERK signaling in the transition from multipotent stem cell to post-mitotic progeny using primary stem cells from the rat embryonic cortex. Fibroblast growth factor-2 (FGF-2) is a stem cell mitogen, whereas platelet-derived growth factor AA (PDGF-AA) expands a pool of committed neuronal precursors from stem cells. When comparing ERK activation by these growth factors, we found that FGF-2 stimulates high and PDGF-AA lower levels of ERK phosphorylation in stem cells. Differentiation was monitored as down-regulation of the bHLH transcription factor mammalian achaete-scute homologue-1 (MASH1). Even in the absence of active ERK, MASH1 became down-regulated and microtubule-associated protein 2-positive cells could form. Thus, ERK activation seems dispensable for the earliest steps of CNS stem cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Blotting, Western
  • Brain / embryology
  • Bromodeoxyuridine / pharmacology
  • Cell Differentiation
  • Central Nervous System / cytology*
  • DNA-Binding Proteins / metabolism
  • Detergents / pharmacology
  • Down-Regulation
  • Enzyme Activation
  • Fibroblast Growth Factor 2 / metabolism*
  • Immunohistochemistry
  • Microtubule-Associated Proteins / metabolism
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / metabolism*
  • Neurons / metabolism*
  • Octoxynol / pharmacology
  • Phosphorylation
  • Platelet-Derived Growth Factor / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction*
  • Time Factors
  • Transcription Factors / metabolism

Substances

  • Ascl1 protein, rat
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Detergents
  • Microtubule-Associated Proteins
  • Platelet-Derived Growth Factor
  • Transcription Factors
  • platelet-derived growth factor A
  • Fibroblast Growth Factor 2
  • Octoxynol
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • Bromodeoxyuridine