| Title | Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. |
| Publication Type | Journal Article |
| Year of Publication | 2000 |
| Authors | Morrison SJ, Perez SE, Qiao Z, Verdi JM, Hicks C, Weinmaster G, Anderson DJ |
| Journal | Cell |
| Volume | 101 |
| Issue | 5 |
| Pagination | 499-510 |
| Date Published | 2000 May 26 |
| ISSN | 0092-8674 |
| Keywords | Animals, Avian Proteins, Bone Morphogenetic Protein 2, Bone Morphogenetic Proteins, Cell Differentiation, Cell Line, Transformed, Chick Embryo, Fibroblasts, Humans, Immunoglobulin Fc Fragments, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Mice, Nerve Tissue Proteins, Neural Crest, Neuregulin-1, Neuroglia, Neurons, Receptors, Cell Surface, Receptors, Notch, Recombinant Fusion Proteins, Recombinant Proteins, Signal Transduction, Solubility, Stem Cells, Transforming Growth Factor beta |
| Abstract | The genesis of vertebrate peripheral ganglia poses the problem of how multipotent neural crest stem cells (NCSCs) can sequentially generate neurons and then glia in a local environment containing strong instructive neurogenic factors, such as BMP2. Here we show that Notch ligands, which are normally expressed on differentiating neuroblasts, can inhibit neurogenesis in NCSCs in a manner that is completely dominant to BMP2. Contrary to expectation, Notch activation did not maintain these stem cells in an uncommitted state or promote their self-renewal. Rather, even a transient activation of Notch was sufficient to cause a rapid and irreversible loss of neurogenic capacity accompanied by accelerated glial differentiation. These data suggest that Notch ligands expressed by neuroblasts may act positively to instruct a cell-heritable switch to gliogenesis in neighboring stem cells. |
| DOI | 10.1016/s0092-8674(00)80860-0 |
| Alternate Journal | Cell |
| PubMed ID | 10850492 |
| Grant List | R01 NS23476 / NS / NINDS NIH HHS / United States |