Wiring the Brain

The traditional view of neural development is linear. First, the embryo and neurectoderm are patterned by secreted factors, which establish cell fates among progenitors and then differentiated neurons, encoded by combinations of transcription factors. The fate or phenotype of each neuron includes the expression of the specific set of ion channels, neurotransmitters and receptors that determine its physiological function. It also includes expression of a particular repertoire of guidance receptors and surface molecules regulating connectivity, which enable axonal pathfinding and target selection. The processes that establish connectivity are usually thought of as happening after the fate of neurons and their targets have been established. This linear paradigm, from patterning to differentiation to connection, has been increasingly challenged by studies from both invertebrate and vertebrate systems. A number of studies have shown that incoming axons can regulate the proliferation an...

Schizophrenia is a common and devastating disorder, involving stable impairments in a wide range of cognitive, sensory and motor domains, as well as fluctuating episodes of psychosis, characterised by disordered thoughts, hallucinations and delusions. Though it tends to emerge as a full-blown disorder in late adolescence or early adulthood, a wealth of evidence supports the model that it is caused by disturbances in neural development at much earlier time-points, including prenatally. Recent neuroimaging analyses have supported psychological theories of schizophrenia as a “disconnection syndrome”, showing altered structural and functional connectivity between (and also within) many regions of the brain. Schizophrenia can thus be thought of as the result of alterations in brain wiring, and these alterations are, in turn, caused by mutations. There is strong and consistent evidence from twin, adoption and family studies that schizophrenia is highly heritable. Though this fact is now...