NCSCs cultured with BMP and Wnt maintain stem cell markers (green and red).
More than a simple blockade to a sensory fate, the combination of Wnt and BMP actually instructs NCSCs to maintain their stem cell qualities. In their presence, all differentiated fates were avoided, and stem cell markers were expressed for days in culture. Upon Wnt withdrawal, NCSCs were then still able to differentiate in response to NRG1, TGFβ, or BMP.
Responsiveness to Wnt, however, was diminished after several days in culture. A few days after emerging from the neural tube, NCSCs in vivo were also less responsive to Wnt. This property might restrict the place and time of sensory neuron formation. Since Wnt is no longer potent, other factors may have to assume control of stem cell maintenance. Or perhaps an early blast of Wnt and BMP sustains stem cells until they find a differentiation signal.
A complex of downstream effectors of BMP and Wnt signaling—Sox and β-catenin, respectively—has been found in bone and endodermal cells. Whether this combination turns on genes for stem cell maintenance in NCSCs remains to be seen.