Abstract
Dysregulation of neural stem cells (NSCs) is associated with several neurodevelopmental disorders, including epilepsy and autism spectrum disorder. The mammalian target of rapamycin (mTOR) integrates the intracellular signals to control cell growth, nutrient metabolism, and protein translation. mTOR regulates many functions in the development of the brain, such as proliferation, differentiation, migration, and dendrite formation. In addition, mTOR is important in synaptic formation and plasticity. Abnormalities in mTOR activity is linked with severe deficits in nervous system development, including tumors, autism, and seizures. Dissecting the wide-ranging roles of mTOR activity during critical periods in development will greatly expand our understanding of neurogenesis.
Highlights
Neurogenesis from the embryonic brain throughout adulthood requires a well-regulated interaction of inductive cues and secreted signals that guide the development of neural stem cells (NSCs)
Many extracellular signals converge on the mammalian target of rapamycin pathway, which is a chief regulator of cell growth, proliferation, and protein translation
Many of the recent studies into the role of the mammalian target of rapamycin (mTOR) complexes have focused on mTOR complex 1 (mTORC1) and control of cap-dependent translation
Summary
Neurogenesis from the embryonic brain throughout adulthood requires a well-regulated interaction of inductive cues and secreted signals that guide the development of neural stem cells (NSCs). For a stem cell to transition into a properly functioning neuron it must process complex external and internal signals to divide, differentiate, migrate, and integrate properly. These stages are guided by extrinsic factors that promote the transcription of genes to define the cell through maturation. Because mutations upstream of the regulators of the mTOR pathway in NSCs lead to hyperactivity in mature neurons, it is important to understand mTOR signaling during nervous system development. We describe our current understanding of the role of mTOR and related pathways at each stage of neurogenesis, focusing on embryonic cortical and postnatal development
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