Distinct glial cell types of the vertebrate peripheral nervous system (PNS) are derived from the neural crest. Here we show that the expression of the Ets domain transcription factor Erm distinguishes satellite glia from Schwann cells beginning early in rat PNS development. In developing dorsal root ganglia (DRG), Erm is present both in presumptive satellite glia and in neurons. In contrast, Erm is not detectable at any developmental stage in Schwann cells in peripheral nerves. In addition, Erm is downregulated in DRG-derived glia adopting Schwann cell traits in culture. Thus, Erm is the first described transcription factor expressed in satellite glia but not in Schwann cells. In culture, the Neuregulin1 (NRG1) isoform GGF2 maintains Erm expression in presumptive satellite cells and reinduces Erm expression in DRG-derived glia but not in Schwann cells from sciatic nerve. These data demonstrate that there are intrinsic differences between these glial subtypes in their response to NRG1 signaling. In neural crest cultures, Erm-positive progenitor cells give rise to two distinct glial subtypes: Erm-positive, Oct-6-negative satellite glia in response to GGF2, and Erm-negative, Oct-6-positive Schwann cells in the presence of serum and the adenylate cyclase activator forskolin. Thus, Erm-positive neural crest-derived progenitor cells and presumptive satellite glia are able to acquire Schwann cell features. Given the in vivo expression of Erm in peripheral ganglia, we suggest that ganglionic Erm-positive cells may be precursors of Schwann cells.
The transcription factor Erm is a member of the Pea3 subfamily of Ets domain proteins that is expressed in multipotent neural crest cells, peripheral neurons, and satellite glia. A specific role of Erm during development has not yet been established. We addressed the function of Erm in neural crest development by forced expression of a dominant-negative form of Erm. Functional inhibition of Erm in neural crest cells interfered with neuronal fate decision, while progenitor survival and proliferation were not affected. In contrast, blocking Erm function in neural crest stem cells did not influence their ability to adopt a glial fate, independent of the glia-inducing signal. Furthermore, glial survival and differentiation were normal. However, the proliferation rate was drastically diminished in glial cells, suggesting a glia-specific role of Erm in controlling cell cycle progression. Thus, in contrast to other members of the Pea3 subfamily that are involved in late steps of neurogenesis, Erm appears to be required in early neural crest development. Moreover, our data point to multiple, lineage-specific roles of Erm in neural crest stem cells and their derivatives, suggesting that Erm function is dependent on the cell intrinsic and extrinsic context.
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