Stem cell scientists at the University of Edinburgh have discovered that Notch, a protein first discovered more than 80 years ago in the fruit fly, directs unspecialized embryonic stem cells to become cells of the nervous system.
These unexpected findings pave the way for using lab-grown cells to model disease and test the effects of new drugs, and are published online this week in the open-access journal PLoS Biology.
Embryonic stem cells have the potential to make all 200 cell types in the body. The challenge is to restrain this diversity and uncover the signals that commit stem cells to a single specialised function. Sally Lowell and her colleagues have now established that Notch gives embryonic stem cells the critical push towards becoming cells of the nervous system.
The researchers show that when Notch is activated in embryonic stem cells, up to 90% of the cells in the dish become nerve cells. In any colony of embryonic stem cells, under normal conditions, many never become cells of the nervous system: they spontaneously change into other cell types or remain as embryonic stem cells.
The Notch effect can be observed in both mouse and human embryonic stem cells, and can be created without any recourse to genetic engineering - all it takes is the presence of Notch activating signals in the cells that stem cells grow on.
As individual embryonic stem cells become specialised, they communicate with those around them. Notch is a major means of communication, and has, according to Dr Lowell, “a domino effect: once it is switched on in a small group of cells, it sets off a wave of Notch activation in neighbouring cells, directing them all to become cells of the nervous system.”