Smith's team has previously established simple culture conditions that enable 60–70% of ES cells in culture to become neural. Interestingly, when using this system, they have noticed that the neural and non-neural cells develop side by side within the same colony (rather than colony by colony), indicating that cell–cell interaction might regulate neural specification. Notch, an important developmental factor, mediates cell fate decisions through cell–cell communication in a number of tissues. To investigate the potential involvement of Notch in neural differentiation, the team used a transgenic approach to overexpress the active intracellular form of Notch (NotchIC) — effectively overriding the cell–cell communication and instead keeping Notch signalling permanently 'switched on'. When these modified ES cells (known as R26NotchIC) were cultured to become neural, induction was considerably more uniform — fewer than 10% of the population were non-neural.
As well as improved neural induction, the team also noticed something different about the non-neural cells of the R26NotchIC culture compared with non-neural cells in control ES culture. When control ES cells underwent neural induction, 10–20% of cells differentiated into other cell types. However, in the R26NotchIC culture only neural cells and a few undifferentiated ES cells were detected. This suggests that Notch not only induces neural fate but also supresses alternative fate decisions.
This is a preview of subscription content, access via your institution