cells that will become neurons. Glial cells, the supporting cells of the nervous system, are also generated, but somewhat later than neurons, between weeks 20 and 40 (de Graaf-Peters and Hadders-Algra, 2006). Once cells are generated, two different processes overlap in time. First, the identity or “fate” of these cells becomes progressively more restricted, until the cells are fully differentiated into a specific type of neuron or glial cell. Second, neurons must travel from the site of their origin to their appropriate final location in the brain to provide the function they will ultimately serve, a process called neuronal migration (de Graaf-Peters and Hadders-Algra, 2006; Levitt, 2003; Rakic, 2003). The precise path of neuronal migration is determined by the timing and position of a cell when it is generated, together with a molecular “map” composed of a variety of molecular signals from neighboring cells that guide the migrating cell to its proper final position in a precise and reproducible manner (de Graaf-Peters and Hadders-Algra, 2006; Levitt, 2003; Rakic, 2003). The number of migrating neurons in the human fetus peaks by about week 20 of gestation, and migration stops by about week 30 (de Graaf-Peters and Hadders-Algra, 2006).
Disturbances in neuronal migration have emerged as a key area of interest in understanding the developmental basis of MEB disorders. Failures in neuronal migration produce an accumulation of neurons in the wrong areas of the brain and, consequently, can lead to disorganized brain structure and function. This can be seen in major malformations of the brain, such as lissencephaly (a brain that lacks the usual, complex folded surface) (Guerrini and Filippi, 2005). More subtle disturbances of neuronal migration can create isolated islands of neurons or disruptions of normal circuit function, leading to seizures (Guerrini and Filippi, 2005). Genetic and environmental influences on neuronal migration can produce even more subtle disturbances in the locations of cells that may not be visible at the gross anatomical level but may nevertheless affect functional circuits. In cortical areas involved in higher-level cognitive functions, these effects potentially can produce subtle changes in the brain’s behavioral, emotional, and cognitive capacities that may not manifest until later in life (Rakic, 2002, 2003).
Once cells are properly differentiated and as they are migrating to their final locations in the brain, they grow extensions, called axons and dendrites, that allow them to connect to and communicate with other neurons. Axons are primarily responsible for sending signals to other cells, and dendrites are processes that primarily receive signals from other cells. Axons use the guidance of external molecular signals to find their way to the right target cells with which they will connect and communicate. A combination