A study of the early Schwann cell lineage : growth factors involved in the survival and maturation of the Schwann cell precursor in vitro
Cells of the Schwann cell lineage are derived from the cells of the neural crest. Schwann cell development, including factors controlling myelination have been studied extensively, but little is known about the development of the glial cells found in early nerves. This work describes an intermediate cell type in the development of Schwann cells from the neural crest, the Schwann cell precursor. Using immunocytochemistry, the molecular phenotype of these cells has been investigated. A study has been made of S100 expression and survival in vitro in defined medium, on cells isolated from E14 to newborn nerves. These experiments show that glial cells isolated from E14-E15 nerves are not neural crest cells. The transition from precursor to Schwann cell occurs rapidly between E15 and E17 in vivo. Death of precursors in defined medium in vitro has been examined using DNA staining and studies of DNA fragmentation. The results indicate that death is by apoptosis, which can be delayed by addition of protein synthesis inhibitors or elevation of cyclic AMP (cAMP). Culture in neurone-conditioned medium suppresses apoptosis. A large number of growth factors have been investigated for survival effects. Three members of the fibroblast growth factor family have been found to promote short-term precursor survival when used in combination with a member of the insulin growth factor family. An extensive investigation has been made of the combinations required for precursor survival, both in the presence and absence of elevated cAMP. Two families of growth factors, Neu differentiation factors (NDFs) and endothelins are shown to promote long-term survival of the precursors. Precursor maturation in these factors has been followed using immunocytochemistry and assays for survival and proliferation. NDFß-2, but not endothelin, promotes maturation of precursors to Schwann cells with a time course similar to that seen in vivo. Addition of endothelin in the presence of NDFß-2 delays maturation. These results indicate that there is likely to be a complex interplay of growth factors controlling Schwann cell precursor survival and generation of Schwann cells during nerve development.