title: Extracellular signal-regulated protein kinase signaling is uncoupled from initial differentiation of central nervous system stem cells to neurons.
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.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Enarsson
authors.forename: Anna
authors.initials: A
authors.lastname: Erlandsson
authors.forename: Helena
authors.initials: H
authors.lastname: Larsson
authors.forename: Karin
authors.initials: K
authors.lastname: Forsberg-Nilsson
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D015153:Blotting, Western; D001921:Brain / Q000196:embryology; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002454:Cell Differentiation; D002490:Central Nervous System / Q000166:cytology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D003902:Detergents / Q000494:pharmacology; D015536:Down-Regulation; D004789:Enzyme Activation; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D017830:Octoxynol / Q000494:pharmacology; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D004268:DNA-Binding Proteins; D003902:Detergents; D016222:Fibroblast Growth Factor 2; D008869:Microtubule-Associated Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D017830:Octoxynol; D010982:Platelet-Derived Growth Factor; D014157:Transcription Factors; C499318:Ascl1 protein, rat; C075278:platelet-derived growth factor A