FGF2 Concentration Regulates the Generation of Neurons and Glia from Multipotent Cortical Stem Cells

Qian, Xueming; Davis, Andrew A.; Goderie, Susan K.; Temple, Sally

doi:10.1016/s0896-6273(01)80048-9

Cited by 422 publications

(337 citation statements)

References 44 publications

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“…This agrees with previous results that undi erentiated neuroectodermal precursors may require higher concentrations of FGF2 or treatment with FCS or conditioned medium for expression of glial phenotypes (Kilpatrick and Bartlett, 1993;Qian et al, 1997) and may also re¯ect the observation that glial phenotypes are rarely observed in PNET and PNET cell lines. It is also interesting that oligodendrocytic markers have not been reported in PNET biopsy specimens although they have been detected in other PNET cell lines (Pietsch et al, 1994).…”

Section: Discussionsupporting

confidence: 92%

“…As yet, this state can only be de®ned as the potential to express neural phenotypes after adhesion on polylysine. This result agrees with previous observations showing that FGF2 is implicated in fate determination of multipotent neural precursor cells (Vescovi et al, 1993;Qian et al, 1997). Furthermore, none of a series of growth factors including EGF, PDGF, CNTF, NGF, BDNF and NT3 could substitute for FGF2 under the culture conditions tested.…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies in vitro have shown that FGF2 can act as a mitogen for central nervous system stem cells (Johe et al, 1996) and pluripotent progenitor cells from embryonic brain (Gritti et al, 1996;Bartlett, 1993, 1995;Qian et al, 1997). In the de®ned medium Dev cells proliferate exponentially with a (7) stained by an anti-MAP kinase antiserum that recognizes both phosphorylated and non-phosphorylated forms of ERK1 and ERK2.…”

Section: Fgf2 Induces Proliferation and Substrate Detachment Of Dev Cmentioning

confidence: 99%

“…Several lines of evidence suggest that they may be derived from pluripotent neural precursors or their immature progeny (Trojanowski et al, 1994;Valtz et al, 1991;McKay et al, 1993;Rorke et al, 1997). Central nervous system (CNS) stem cells and multipotent precursors have been identi®ed by lineage studies using retroviral labels in vivo and in vitro as well as subcloning studies in dispersed cell cultures of developing and adult brain (Reid et al, 1995;Stemple and Mahanthappa, 1997;Qian et al, 1997). They are capable of proliferation and di erentiation with neuronal, oligodendrocytic and astrocytic fates.…”

Section: Introductionmentioning

confidence: 99%

“…Basic ®broblast growth factor (FGF2) stimulates the proliferation and di erentiation of multipotent CNS stem cells by as yet unidenti®ed mechanisms (Johe et al, 1996;Vescovi et al, 1993;Gritti et al, 1996;Qian et al, 1997) and is present in FCS. FGF receptors (FGFR) have been identi®ed in undi erentiated neuroepithelial cells in vivo and in vitro (Peters et al, 1993;Miyake et al, 1995) and in PNET (Weiner et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Human primitive neuroectodermal tumour cells behave as multipotent neural precursors in response to FGF2

Dufay

Rudkin

et al. 1998

Oncogene

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Primitive neuroectodermal tumours (PNET) are thought to derive from the malignant transformation of pluripotent CNS precursors although this hypothesis has yet to be tested in vitro. Here we show that cells of a human PNET cell line`Dev' express functional ®broblast growth factor (FGF) receptors (FGFR) and respond to FGF2 as multipotent CNS precursors. FGF2 induces tyrosine phosphorylation of FGFR-1 and FGFR-2 and many cellular substrates including MAP kinases and stimulates proliferation. Cells detach from plastic substrates and proliferate to form large clusters of undi erentiated cells. After adhesion to polylysine, cells migrate out from the clusters and di erentiate. The majority of di erentiated cells express neuronal phenotypes but distinct subpopulations express oligodendrocytic and astrocytic markers. Mature neural di erentiation markers are not otherwise detected in Dev cells in de®ned medium. Identical results were obtained with 12 monoclonal subclones as well as the parent cell line, con®rming that Dev cells are multipotent. This extends evidence that multipotent CNS precursors are the cellular substrate from which certain PNET develop and shows that FGF2 is a potent proliferation and di erentiation inducer for PNET cells in vitro, suggesting that FGF2 may also modulate the evolution of PNET in vivo. Finally our results suggest that PNET cell lines may provide models to elucidate the biology of human multipotent CNS precursors.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

Section: Fgf2 Induces Proliferation and Substrate Detachment Of Dev Cmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Human primitive neuroectodermal tumour cells behave as multipotent neural precursors in response to FGF2

Dufay

Rudkin

et al. 1998

Oncogene

View full text Add to dashboard Cite

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Emergence of oligodendrocytes from human neural spheres

Murray

Dubois‐Dalcq

1997

J. Neurosci. Res.

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To study the development of human oligodendrocyte precursors (OP), we expanded human embryonic brain-derived neural precursors into spheres with basic fibroblast growth factor (FGF2). Over 90% of the cells in the expanded spheres were precursors coexpressing nestin and the polysialylated (PSA) form of NCAM. The remaining cells were mostly astrocytes and neuronal cells located at the periphery of the floating spheres. When spheres were allowed to adhere on fibronectin-coated substrate in the absence of FGF2, neural precursors migrated in the outgrowth and often formed chains of cells expressing high levels of PSA-NCAM. Many migrating cells also expressed beta-3 tubulin while only scattered elongated cells radiating from the spheres were GFAP+ astrocytes. Spindle-shaped cells not associated with the chains were labeled for the PDGF-alpha receptor and often coexpressed MAP2 neuronal isoforms. Neuronal cells in the outgrowth rapidly established a rich neuritic network where OP expressing O4 and DM20/proteolipid antigens appeared. T3 treatment of neural spheres increased the rate of OP formation and the complexity of their shape. Thus, the generation of human oligodendrocytes from neural precursors is tightly correlated with growth of neuronal processes and enhanced by hormonal signals.

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Opposing mitogenic regulation by PACAP in sympathetic and cerebral cortical precursors correlates with differential expression of PACAP receptor (PAC1-R) isoforms

Zhou

DiCicco‐Bloom

1998

J. Neurosci. Res.

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Neurogenesis in the peripheral and central nervous systems proceeds in region-specific fashion, although underlying mechanisms remain undefined. Emerging evidence indicates that the neuropeptide PACAP and its G-protein-coupled receptor are expressed widely in the embryonic brain, suggesting that the ligand/receptor system plays a role in development. We found previously that PAC1-R activation elicited opposing mitogenic effects in neurogenetic cultures, stimulating peripheral sympathetic neuroblasts while inhibiting cerebral cortical precursors. We have now defined the expression of PAC1-R mRNA isoforms and activation of second-messenger pathways in these model populations. Sympathetic neuroblasts express the "hop" receptor isoform, through which PACAP elicits increased levels of cAMP and activation of the PI signaling pathway. In contrast, cerebral cortical precursors express primarily the "short" (non-insert) receptor isoform and exhibit increased cAMP levels alone following PACAP treatment. Thus, opposing mitogenic regulation in sympathetic and cortical precursors correlates with differential receptor isoform expression and distinct second-messenger signaling. In addition to receptor, PACAP ligand mRNA was expressed by both populations, suggesting that the peptide is produced and acts locally to regulate precursor proliferation. These observations indicate that the PACAP ligand/receptor system is expressed in both the peripheral and central nervous system during development. More generally, these studies suggest that widely expressed extracellular factors mediate region-specific neurogenesis by activating lineage-restricted receptor isoforms and intracellular pathways.

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FGF2 Concentration Regulates the Generation of Neurons and Glia from Multipotent Cortical Stem Cells

Cited by 422 publications

References 44 publications

Human primitive neuroectodermal tumour cells behave as multipotent neural precursors in response to FGF2

Human primitive neuroectodermal tumour cells behave as multipotent neural precursors in response to FGF2

Emergence of oligodendrocytes from human neural spheres

Opposing mitogenic regulation by PACAP in sympathetic and cerebral cortical precursors correlates with differential expression of PACAP receptor (PAC1-R) isoforms

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