P0 and PMP22 mark a multipotent neural crest-derived cell type that displays community effects in response to TGF-beta family factors

Protein zero (PO) and peripheral myelin protein 22 (PMP22) are most promine ntly expressed by myelinating Schwann cells as components of compact myelin of the peripheral nervous system (PNS), and mutants affecting PO and PMP22 show severe defects in myelination, Recent expression studies suggest a ro le of PO and PMP22 not only in myelination hut also during embryonic develo pment, Here we show that, in dorsal root ganglia (DRG) and differentiated n eural crest cultures, PO is expressed in the glial lineage whereas PMP22 is also detectable in neurons, In addition, however, PO and PMP22 are both ex pressed in a multipotent cell type isolated from early DRG. Like neural cre st stem cells (NCSCs), this P0/PMP22-positive cell gives rise to glia, neur ons and smooth-muscle-like cells in response to instructive extracellular c ues. In cultures of differentiating neural crest, a similar multipotent cel l type can be identified in which expression of PO and PMP22 precedes the a ppearance of neural differentiation markers. Intriguingly, this P0/PMP22-po sitive progenitor exhibits fate restrictions dependent on the cellular cont ext in which it is exposed to environmental signals. While single P0/PMP22- positive progenitor cells can generate smooth muscle in response to factors of the TGF-beta family, communities of P0/PMP22-positive cells interpret T GF-beta factors differently and produce neurons or undergo increased cell d eath instead of generating smooth-musclelike cells, Our data are consistent with a model in which cellular association of postmigratory multipotent pr ogenitors might be involved in the suppression of a nonneural fate in formi ng peripheral ganglia.