Brain Development

Mouse models have been central to achieving our current understanding of the molecular and cellular mechanisms underpinning brain development. Brain morphogenesis follows an integrated series of developmental steps: neural induction, neurulation, proliferation, migration, regionalization, axonal outgrowth, synaptogenesis, differentiation, and apoptosis. The most rostral portion of the neural tube, the telencephalon, expands to form the cerebral cortex. The telencephalon engulfs the topologically more caudal diencephalon, within which the thalamus forms. These structures are specified before midgestation, and their cells are generated from E10 to E17. The cerebellum develops from the rostral part of the hindbrain (the metencephalon), and its primordium is specified later than that of other brain regions. Cells migrate radially and tangentially from their sites of origin to generate these structures; this process is only completed postnatally. Cell diversity is the result of differential and combinatorial transcription factor expression in various sectors of the germinal zone at various times. As connections form between nerve cells to initiate the formation of neural circuits, and their electrical properties emerge, the brain begins to process information and to mediate behaviors even during embryonic life. Interactions with the external environment update and adapt the brain’s functional architecture, particularly during critical periods of development, as exemplified by barrel formation, as well as on a continuous basis throughout life. The mechanisms for these later plastic changes are probably a continuation of the processes that sculpt the brain during development. Studies using transgenic mouse models will continue to elucidate the mechanisms that produce the normal and abnormal mammalian brain.