Schwann cell development in embryonic mouse nerves

Previously we proposed that Schwann cell development from the neural crest is a two-step process that involves the generation of one main intermediate cell type, the Schwann cell precursor. Until now Schwann cell precursors h ave only been identified in the rat, and much remains to be learned about t hese cells and how they generate Schwann cells, Here we identify this cell in the mouse and analyze its transition to form Schwann cells in terms of t iming, molecular expression, and extracellular signals and intracellular pa thways involved in survival, proliferation, and differentiation. In the mou se, the transition from precursors to Schwann cells takes place 2 days earl ier than in the rat, i.e., between embryo days 12/13 and 15/16, and is acco mpanied by the appearance of the O4 antigen and the establishment of an aut ocrine survival circuit. Beta neuregulins block precursor apoptosis and sup port Schwann cell generation in vitro, a process that is accelerated by bas ic fibroblast growth factor 2. The development of Schwann cells from precur sors also involves a change in the intracellular survival signals utilized by neuregulins: To block precursor death neuregulins need to signal through both the mitogen-activated protein kinase and the phosphoinositide-3-kinas e pathways although neuregulins support Schwann cell survival by signaling through the phosphoinositide-3-kinase pathway alone, Last, we describe the generation of precursor cultures from single 12-day-old embryos, a prerequi site for culture studies of genetically altered precursors when embryos are non-identical with respect to the transgene in question. J, Neurosci, Res. 56:334-348, 1999, (C) 1999 Wiley-Liss, Inc.