title: Immature neurons from CNS stem cells proliferate in response to platelet-derived growth factor.
abstract: Identifying external signals involved in the regulation of neural stem cell proliferation and differentiation is fundamental to the understanding of CNS development. In this study we show that platelet-derived growth factor (PDGF) can act as a mitogen for neural precursor cells. Multipotent stem cells from developing CNS can be maintained in a proliferative state under serum-free conditions in the presence of fibroblast growth factor-2 (FGF2) and induced to differentiate into neurons, astrocytes, and oligodendrocytes on withdrawal of the mitogen. PDGF has been suggested to play a role during the differentiation into neurons. We have investigated the effect of PDGF on cultured stem cells from embryonic rat cortex. The PDGF alpha-receptor is constantly expressed during differentiation of neural stem cells but is phosphorylated only after PDGF-AA treatment. In contrast, the PDGF beta-receptor is hardly detectable in uncommitted cells, but its expression increases during differentiation. We show that PDGF stimulation leads to c-fos induction, 5'-bromo-2'deoxyuridine incorporation, and an increase in the number of immature cells stained with antibodies to neuronal markers. Our findings suggest that PDGF acts as a mitogen in the early phase of stem cell differentiation to expand the pool of immature neurons.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Erlandsson
authors.forename: M
authors.initials: M
authors.lastname: Enarsson
authors.forename: K
authors.initials: K
authors.lastname: Forsberg-Nilsson
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001973:Bromodeoxyuridine; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D008869:Microtubule-Associated Proteins; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D001973:Bromodeoxyuridine