Neural stem cells have been heralded as a potential therapy to rebuild injured and diseased brain tissue, but to achieve that vision, researchers must decipher the molecular signals that direct the cells to migrate through the brain and mature into different types of brain cells. This signaling network is turning out to have some surprising complexities. In studies presented this week at the American Neurological Association meeting in Boston, Massachusetts, Mark Mehler and colleagues at the Albert Einstein College of Medicine reported that early in neural development, bone morphogeneic proteins (BMPs) direct stem cells down the pathway to becoming neurons, while at the same time inhibiting the processes that would turn them into glial cells. "This demonstration of the simultaneous roles of single growth factors in orchestrating both positive and negative fate decisions from neural stem cells has not been previously envisioned," said Mehler. The team showed that BMPs activate ID2 and ID4, members of the inhibitor of differentiation family, to constrain immature stem cells to become neurons. However, later in cortical development, BMPs play a very different role, directing cells toward becoming a type of glial cell. Untangling this signaling network is obviously important to understanding neurodevelopmental disorders such as epilepsy and mental retardation, and also may be key to harnessing stem cells to treat brain and spinal cord injury and neurodegenerative disorders such as Alzheimer's and Parkinson's.—June Kinoshita

 

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