Grant: Project Grant

The cerebral cortex is the most complex structure within the mammalian brain and plays a key role in consciousness, perception, learning, and memory. These higher-order functions rely on hundreds of different types of nerve cells (neurons) that have distinct molecular and functional characteristics. Interestingly, distinct neuron subtypes are all made from a relatively homogeneous group of neural stem cells. However, what controls neural stem cells to specifically produce one type of neuron over another and how specific identity is ultimately determined is still largely a mystery. It is generally thought that the process is initiated by the activation of specific identity genes in the cell's nucleus, which involves making an RNA copy of the gene. Nevertheless, evidence from our recent studies has revised this simplified view by showing that a critical decision point is the "translation" of that RNA into the corresponding protein. We have recently identified a novel gene that regulates the decision of where and when translation occurs. In this proposed study, we will further explore the mechanisms that underlie the translational regulation of neuronal subtype specification. Our work will be relevant to neurological diseases, such as autism spectrum disorder, and will have other important implications for human health.