Regulation of neural stem cell differentiation in the forebrain
| Autor: | Mark Murphy, Trevor J. Kilpatrick, Clare Faux, Perry F. Bartlett, Ann M. Turnley, Gordon J.f. Brooker, Renée Dutton |
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| Rok vydání: | 1998 |
| Předmět: |
Leukemia Inhibitory Factor Receptor alpha Subunit
Receptors OSM-LIF Cellular differentiation Immunology Bone Morphogenetic Protein 2 Leukemia inhibitory factor receptor Bone Morphogenetic Protein 4 Biology Leukemia Inhibitory Factor Astrocyte differentiation Interferon-gamma Mice Prosencephalon Transforming Growth Factor beta Receptors Opioid delta Glial Fibrillary Acidic Protein Immunology and Allergy Animals Receptors Cytokine Neurons Lymphokines Interleukin-6 Stem Cells Neurogenesis Cell Differentiation Cell Biology Oligonucleotides Antisense Neural stem cell Growth Inhibitors Cell biology Fibroblast Growth Factors Astrocytes Bone Morphogenetic Proteins Neuron differentiation Proteoglycans Stem cell Leukemia inhibitory factor |
| Zdroj: | Immunology and cell biology. 76(5) |
| ISSN: | 0818-9641 |
| Popis: | In the developing forebrain, mounting evidence suggests that neural stem cell proliferation and differentiation is regulated by growth factors. In vitro in the presence of serum, stem cell proliferation is predominantly mediated by fibroblast growth factor-2 (FGF-2) whereas neuronal differentiation can be triggered by FGF-1 in association with a specific heparan sulphate proteoglycan. On the other hand, astrocyte differentiation in vivo and in vitro appears to be dependent on signalling through the leukaemia inhibitory factor receptor (LIFR). The evidence suggests that in the absence of LIFR signalling, the stem cell population is present at approximately the same frequency and can generate neurons but is blocked from producing astrocytes that express glial fibrillary acidic protein (GFAP) or have trophic functions. The block can be overcome by other growth factors such as BMP-2/4 or interferon-gamma, providing further evidence that the inhibition to astrocyte development does not result from loss of a precursor population. Signalling through the LIFR, in addition to stimulating astrocyte differentiation, may also inhibit neuronal differentiation, which may explain why this receptor is expressed at the earliest stages of neurogenesis. Another signalling system which also exerts its influence on neurogenesis through active inhibition is Delta-Notch. We show in vitro that at high cell densities which impede neuronal production by FGF-1, lowering the levels of expression of the receptor Notch by antisense oligonucleotide results in a significant increase in neuronal production. Thus, stem cell differentiation appears to be dependent on the outcome of interactions between a number of signalling pathways, some which promote specific lineages and some which inhibit. |
| Databáze: | OpenAIRE |
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