Monday, October 26, 2009

Cortical Development

Cortical development is the development of the cerebral cortex from the embryo state to maturity. It is very important to understand the mechanisms of cortical development, because it supplies us with the insight into the pathogenesis of many genetic and acquired developmental psychiatric disorders, which include autism, schizophrenia and learning disabilities.

The adult human cerebral cortex has six neuronal layers, each consisting of specialized neurons with specific phenotypes and synaptic connections. In the majority of organs, cells are born near their eventual location, but in the embryonic cortical development neurons are generated some distance away. The final migration of these nerve cells and the establishment of proper interneuronal connections are critical for proper cortical functioning. Faults in this dynamic process provoke a number of developmental disorders of higher brain function.

During the embryonic development of the cortex, the first neurons destined to settle in the human cortex are produced during the first half of gestation, deep within the cerebrum and close to the cavity of the cerebral ventricles, in a area called the ventricular zone. Shortly after their last mitotic divisions, these neurons migrate outward toward the pial surface of the cortex where they make up a sheet of nerve cells called the cortical plate. Each successive generation of migrating neurons passes through the previously born cells before arriving at the final destination at the interface between the cortical plate and the marginal zone.

Neurons use a transient population of radial glial cells during migration as a scaffolding to aid their navigation. These glial cells form long fascicles that span the cerebral cortex and guide the migrating neurons through each cortical layer. According to the radial unit hypothesis of cortical development, the horizontal location of cortical neuron is determined by the position of its precursor cells in the proliferative ventricular zone, while its depth results from its birth order.

First, the cortex develops in an inside-out pattern in which the earliest born neurons are found in the deepest cortical layers while the later born neurons move to the more superficial layers. Second, the radial glial hypothesis provides an explanation for the columnar organization of the cortex. Each group of progenitor cells within the ventricular zone gives rise to a column of interrelated neurons above it. After the neurons have taken their proper laminar positions, they develop characteristic synaptic connections with nearby neurons as well as more distant neurons in associated regions of the cortex.

Phylogenetically, the sequence in which the cortex develops agrees with regionally relevant milestones in cognitive and functional development. Parts of the brain associated with more basic functions matured early: motor and sensory brain areas matured first, followed by areas involved in spatial orientation, speech and language development, and attention (upper and lower parietal lobes). Later to mature were areas involved in executive function, attention, and motor coordination (frontal lobes).