Schwann cell development in embryonic mouse nerves

Abstract

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 have only been identified in the rat, and much remains to be learned about these 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 timing, molecular expression, and extracellular signals and intracellular pathways involved in survival, proliferation, and differentiation. In the mouse, the transition from precursors to Schwann cells takes place 2 days earlier than in the rat, i.e., between embryo days 12/13 and 15/16, and is accompanied by the appearance of the 04 antigen and the establishment of an autocrine survival circuit. Beta neuregulins block precursor apoptosis and support Schwann cell generation in vitro, a process that is accelerated by basic fibroblast growth factor 2. The development of Schwann cells from precursors 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-kinase 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 prerequisite for culture studies of genetically altered precursors when embryos are non-identical with respect to the transgene in question.

Adult rat bone marrow stromal cells differentiate into Schwann cell-like cells in vitro

“…HRG was also reported to induce neural crest cells to develop selectively into SCs via MAPK signaling pathway (Adlkofer and Lai 2000;Zanazzi et al 2001;Leimeroth et al 2002;Joseph et al 2004;Maro et al 2004;Chen et al 2006a;Ogata et al 2006). The use of HRG together with bFGF might yield synergetic effects to block SC precursor death and support the maturation of precursors to generate SCs (Zorick et al 1996;Dong et al 1999;Jessen et al 2002, Rosenbaum et al 1997. PDGF can activate MAP kinase in MSCs and FSK can stimulate the expression of growth factor receptors and upregulate the intracellar cAMP level to enhance mitogenic responses at an early stage.…”

Perinatal or Adult Nf1 Inactivation Using Tamoxifen-Inducible PlpCre Each Cause Neurofibroma Formation

“…Neural crest cells develop into Schwann cell precursors between E11 and E13 in mouse sciatic nerve, and Schwann cells by E18 (11-12). Progenitors identified after the establishment of the dorsal root ganglia (DRG) have more limited self-renewal and differentiation potential than neural crest stem cells (13-17).…”

Nf1 Mutation Expands an EGFR-Dependent Peripheral Nerve Progenitor that Confers Neurofibroma Tumorigenic Potential

“…Neural crest cells develop into Schwann cell precursors between E11 and E13 in mouse sciatic nerve, immature Schwann cells by E15, and Schwann cells by E18 (Dong et al, 1999; Jessen and Mirsky, 2005). Progenitors identified after the establishment of the dorsal root ganglia (DRG) and the peripheral nerve have more limited self-renewal and differentiation potential than neural crest stem cells (Bixby et al, 2002; Kleber et al, 2005; Nagoshi et al, 2008).…”

“…Progenitors identified after the establishment of the dorsal root ganglia (DRG) and the peripheral nerve have more limited self-renewal and differentiation potential than neural crest stem cells (Bixby et al, 2002; Kleber et al, 2005; Nagoshi et al, 2008). Products of the neuregulin-1 ( Nrg-1 ) gene, acting through the receptor tyrosine kinase heterodimer ErbB2/3, promote survival of Schwann cell precursors and their differentiation into S100β + Schwann cells (Dong et al, 1999; Leimeroth et al, 2002; Shah et al, 1996). The roles of most growth factors have not been analyzed in the developing PNS, especially in the neural crest-Schwann cell precursor transition.…”