Neural crest progenitors and stem cells

Abstract

In the vertebrate embryo, multiple cell types originate from a common structure, the neural crest (NC), which forms at the dorsal tips of the neural epithelium. The NC gives rise to migratory cells that colonise a wide range of embryonic tissues and later differentiate into neurones and glial cells of the peripheral nervous system (PNS), pigment cells (melanocytes) in the skin and endocrine cells in the adrenal and thyroid glands. In the head and the neck, the NC also yields mesenchymal cells that form craniofacial cartilages, bones, dermis, adipose tissue, and vascular smooth muscle cells. The NC is therefore a model system to study cell diversification during embryogenesis and phenotype maintenance in the adult. By analysing the developmental potentials of quail NC cells in clonal cultures, we have shown that the migratory NC is a collection of heterogeneous progenitors, including various types of intermediate precursors and highly multipotent cells, some of which being endowed of self-renewal capacity. We also have identified common progenitors for mesenchymal derivatives and neural/melanocytic cells in the cephalic NC. These results are consistent with a hierarchical model of lineage segregation wherein environmental cytokines control the fate of progenitors and stem cells. One of these cytokines, the endothelin3 peptide, promotes the survival, proliferation, and self-renewal capacity of common progenitors for glial cells and melanocytes. At post-migratory stages, when they have already differentiated, NC-derived cells exhibit phenotypic plasticity. Epidermal pigment cells and Schwann cells from peripheral nerves in single-cell culture are able to reverse into multipotent NC-like progenitors endowed with self-renewal. Therefore, stem cell properties are expressed by a variety of NC progenitors and can be re-acquired by differentiated cells of NC origin, suggesting potential function for repair.