Brain size is controlled by the mammalian target of rapamycin (mTOR) in mice

The number of neurons in the brain is mostly determined by neural progenitor proliferation and neurogenesis during embryonic development. Increase in postnatal brain size is largely dependent on cellular volume changes. The mammalian target of rapamycin (mTOR) signaling has been associated with cell proliferation and size determination in a variety of cell types. The role of mTOR signaling in neural development has been increasingly pursued due to its association with neurodevelopmental disorders and cancers. Surprisingly, however, there has been lack of in vivo genetic evidence that defines mTOR functions in neural progenitors during progenitor self-renewal and subsequent brain formation. Here, we discuss our recent evidence that mTOR signaling is required for the establishment of normal brain size during development. Mice lacking mTOR show smaller brain and reduced numbers of neural progenitors and neurons. Additionally, mTOR interacts with the Wnt signaling pathway in the control of neural progenitors. Our study establishes the mTOR signal as a key regulator of an evolutionarily conserved cascade that is responsible for vertebrate brain size.