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

T he number of neurons in the brainis mostly determined by neural progenitor proliferation and neurogene-sis 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 determi-nation in a variety of cell types. The role of mTOR signaling in neural develop-ment has been increasingly pursued due to its association with neurodevelopmen-tal 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 inter-acts with the Wnt signaling pathway in the control of neural progenitors. Our study establishes the mTOR signal as a key regulator of an evolutionarily con-served cascade that is responsible for ver-tebrate brain size