The growth factor Activin is key for regulating the differentiation of neural stem cells into a specialised population of interneurons in the brain. These findings, reported in Nature Communications this week, provide new insight into the mechanisms which determine the fate of stem cell pools, which are being investigated for their therapeutic potential in a number of diseases.
The fate of stem cells is dependent upon the balance of different signalling pathways which contribute to proliferation and development into different populations of cells. The growth factor Activin is highly expressed in the brain, suggesting that it plays important roles in these processes.
Tristan Rodriguez and colleagues use certain neural precursors derived from mouse and human embryonic stem cells to show that the interplay between Activin and the Sonic Hedgehog signalling pathway controls the decision of neural precursors to self-renew or differentiate. Specifically, they find that Activin controls differentiation by inhibiting the Sonic Hedgehog signalling pathway whilst enhancing the retinoic acid pathway which promotes neurogenesis.
They also show that Activin selectively promotes differentiation to a population of cortical interneurons. Since the loss of these interneurons has been implicated in neuropsychiatric illnesses such as epilepsy, autism and schizophrenia, the authors suggest that these findings could be used to develop novel therapies in neuroregenerative medicine.