Developmental Biology

Stem Cells Become Glia in Response to Notch

Science's STKE  06 Jun 2000:
Vol. 2000, Issue 35, pp. tw2
DOI: 10.1126/stke.2000.35.tw2

Stem cells in the mammalian neural crest (NCSCs) can differentiate into neurons, glia, or smooth muscle cells. As the peripheral nervous system is formed, migrating NCSCs first differentiate into neurons in response to neurogenic factors like the BMPs (bone morphogenetic proteins); later, in spite of continued exposure to BMPs, the NCSCs form glial cells (which surround the cell bodies of the neurons). But what signals orchestrate the switching of these multipotent NCSCs from one to another distinct cell fate? Morrison et al. show that a key factor is likely to be signaling through the receptor Notch. They used cultured NCSCs from rat to show that exposure to a soluble form of the Notch ligand, Delta-1, could inhibit neurogenesis induced by BMP2 and could promote formation of glial cells. Surprisingly, this effect of Notch activation was irreversible and cell heritable. This was unexpected because in Drosophila and Xenopus model systems, Notch appears to work differently--only transiently and reversibly inhibiting differentiation, leaving stem cells competent to assume multiple fates. In the mammalian system, it seems that the initial differentiation of neurons, which themselves express Notch ligands, can trigger the sequential formation of glia by activating Notch signals in neighboring stem cells. These signals appear to inhibit the capacity of the NCSCs to form neurons while instructing them to adopt a glial cell fate.

Morrison, S.J., Perez, S.E., Qiao, Z., Verdi, J.M., Hicks, C., Weinmaster, G., and Anderson, D.J. (2000) Transient Notch activation initiates an irreversible switch from neurogenesis to gliogenesis by neural crest stem cells. Cell 101: 499-510. [Online Journal]