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1 Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; and
2 Biovitrum AB, Stockholm, Sweden
Requests for reprints: Karin Forsberg-Nilsson, Department of Medical Biochemistry and Microbiology, Box 582, Biomedical Center, Uppsala University 75123 Uppsala, Sweden. Phone: 46-18-471-4158; Fax: 46-18-471-4244. E-mail: karin.nilsson{at}imbim.uu.se
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.
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