During early development, neurons migrate along a short and direct route, using a transient population of radial glial cells as a sort of scaffolding. Later, however, as the cerebral cortex begins to fold, the route becomes longer and more complex, the later migrating neurons assuming positions external or more superficial to those that arrived earlier. Thus, layer 2 neurons are generated and migrate later than layers 3, 4, 5 and 6. The deepest layers are the first to develop first, which results in an ‘inside-out, outside-last’ pattern of migration. All neurons of ‘higher’ vertebrate CNS are born in one place and migrate to another. In the spinal cord and parts of the brain stem, neurones are born near the ventricular surface, and then migrate in a radial, or vertical, direction away from this surface. However, they stop short of the outer pail surface and differentiate in this position. The outermost zone remains free of neuron cell bodies, and instead becomes populated by axons. Consequently, in the adult spinal cord and much of the brain stem, gray matter is inside and white matter is outside. The forebrain has three basic patterns of migration:
• some neurons migrate vertically and stop short of the pial surface, just as in the spinal cord. They differentiate in this deep position to form most of the thalamus, hypothalamus, and limbic parts of the forebrain.
• other neurons migrate vertically, but do not stop short as they migrate all the way out to the pail surface, where they form a layer of cells referred to as the cortical plate due to its location at the brain surface. The hippocampus begins as a simple cortical plate with one layer of cells, and never adds additional cellular layers (even though it continues to generate neurones through the life span). The cerebral isocortex begins development like the hippocampus. However, in the isocortex, there are several waves of later migrations, which travel vertically past the first arrivals, and thereby creating a cortex that has not one but multiple layers of neurons.
• still other neurons leave the ventricular surface, but continue to divide. Their migrations before and after their ‘birthdays’ are usually horizontal or tangential rather than radial. These cells form the caudate nucleus, the putamen (both in the basal ganglia), the pulvinar of the thalamus, and the horizontally connecting cells in the isocortex.
While cell migration is largely a prenatal phenomenon, it does continue postnatally in a limited number of areas of the brain, one example being the hypothalamus. Abnormalities in neuronal migration are linked to a number of developmental disorders such as lissencephaly and those concerning the control of movement (e.g., cerebral palsy). Both dyslexia and schizophrenia have been ascribed to more subtle abnormalities in migration and in the development of synaptic connections. The molecular or genetic bases for these abnormalities are being revealed at an increasing rate using techniques like forward genetics in mice. For example two genes,FLN1 and ARFGEF2, are necessary for migration to start, and if they are mutated they never leave the proliferating ventricular zone. Another example is reelin, that normally arrests neurons in their appropriate places, but if mutated results in abnormal forms of locomotion among other things. In fact, it seems that there are a range of genes responsible for starting, maintaining and completing migration.
See Basal ganglia (development), Brain stem, Cajal-Retius cells, Cerebellum (development), Cerebral cortex (development), Cerebral cortex (disorders), Cerebral palsy, Dyslexia, Flagella, Forward genetics, Glial cells, Gray matter, Hippocampus, Hypothalamus, Isocortex, Lissencephaly, Netrins, Neuroblasts, Neurogenesis, Neuronal migration disorders, Organogenesis, Plexus, Plial surface, Proliferative ventricular zone, Radial glia cells, Reelin, Spinal cord, Thalamus, White matter