| First Author | Dias JM | Year | 2014 |
| Journal | Neuron | Volume | 84 |
| Issue | 5 | Pages | 927-39 |
| PubMed ID | 25467979 | Mgi Jnum | J:217450 |
| Mgi Id | MGI:5614127 | Doi | 10.1016/j.neuron.2014.10.033 |
| Citation | Dias JM, et al. (2014) Tgfbeta signaling regulates temporal neurogenesis and potency of neural stem cells in the CNS. Neuron 84(5):927-39 |
| abstractText | How the sequential specification of neurons and progressive loss of potency associated with aging neural progenitors are regulated in vertebrate brain development is poorly understood. By examining a temporal differentiation lineage in the hindbrain, we here identify Tgfbeta as a switch signal that executes the transition between early and late phases of neurogenesis and concurrently constrains progenitor potency. Young progenitors have inherent competence to produce late-born neurons, but implementation of late-differentiation programs requires suppression of early identity genes achieved through temporally programmed activation of Tgfbeta downstream of Shh signaling. Unexpectedly, we find that sequentially occurring fate-switch decisions are temporally coupled, and onset of Tgfbeta signaling appears thereby to impact on the overall lifespan of the temporal lineage. Our study establishes Tgfbeta as a regulator of temporal identity and potency of neural stem cells, and provides proof of concept that Tgfbeta can be applied to modulate temporal specification of neurons in stem cell engineering. |
