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• W840341305 abstract "The first part of the studies presented in this thesis shows that NDFβ (but not NDFα),a member of a novel family of growth factors, acts as a long-term survival factor forSchwann cell precursors. The potential of NDFβ to rescue precursors from apoptoticcell death is independent of activation of either IGF receptors or insulin receptors. Incontrast, FGF in the presence of IGF only supports precursor survival for 20 hr. Theloss of survival activity of this factor in long-term precursor cultures may be due tothe fact that precursors lose their responsiveness to FGF. NDFβ not only rescuesprecursors from apoptotic cell death but also stimulates DNA synthesis in these cells.The mitogenic potential generated by this factor is also independent of both activationof IGF receptors and elevation of cAMP levels. FGF in combination with forskolin, awell known Schwann cell mitogen combination, fails to promote DNA synthesis inSchwann cell precursors. Interestingly, TGFβ acts as a mitogen but not survival factorfor these cells. Schwann cell precursors cultured in NDFβ containing medium notonly survive, but also develop into Schwann cells as judged by their ability to survivein defined medium and expression of S100. Furthermore, this study also demonstratesthat Schwann cell precursors express the NDF receptors: ErbB2 and ErbB4.The ability of NDF to regulate survival and DNA synthesis in Schwann cell precursors suggests that this molecule may play an important role in the interactionbetween neurons and precursors. The second part of the thesis shows that both pureneuron conditioned medium and neuronal surface molecules support Schwann cellprecursor survival, and neurons, but not Schwann cell precursors, express NDFprotein. A soluble ErbB4 protein blocks the survival activity in neuron conditionedmedium and that associated with neuronal surfaces, indicating that NDF acts asneuro-glia signalling molecule, mediating precursor survival. Furthermore, the neuronal signals also induce DNA synthesis in Schwann cell precursors and drive thematuration and differentiation of these cells in the neuron-precursor co-cultures.The third part of the thesis demonstrates that two different mitogenic assays may giveinformation that can be related to two different proliferation events, i. e. during nervedevelopment and during Wallerian degeneration. In the first assay, using cells whichare assayed immediately after dissociation from nerves, FGF, NDF, TGFβ and PDGFhave differing mitogenic activities which may reflect the mitogenic activity of thesefactors in normal nerve. In the second assay, using Schwann cells pre-cultured inserum-containing medium for 5 days, all the factors mentioned above are mitogenic,and the DNA synthesis stimulated by these factors is higher in adult Schwann cellsthan younger cells, which is in line with the massive proliferation of adult Schwanncells seen in Wallerian degeneration." @default.
• W840341305 created "2016-06-24" @default.
• W840341305 creator A5085348830 @default.
• W840341305 date "1996-01-01" @default.
• W840341305 modified "2023-09-28" @default.
• W840341305 title "A study of schwann cell survival, proliferation and interaction with neurons" @default.
• W840341305 hasPublicationYear "1996" @default.
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