The Corpus Callosum

Written by Professor Linda J. Richards, Queensland Brain Institute, Australia. 2013

The basic building blocks of the brain are cells called neurons. Neurons are specialized cells that communicate with one another via electrical activity and chemical neurotransmitters.

Each neuron has three main compartments;

1) a cell body, with a nucleus containing DNA,

2) processes called dendrites (treelike processes) that receive information from other neurons and

3) an axon that transmits information from the neuron to other neurons in the brain.

There are approximately 100 billion neurons in the human brain and each of these neurons is connected to other neurons through these dendrites and axons or fibres (similar to the electrical wires of an electric circuit).

The corpus callosum is a big bundle of axons that connects neurons in the left and right cerebral hemispheres. In fact, it is the largest fibre tract in the brain.

Generally, the fibres are arranged in an ordered fashion from anterior to posterior (front to back) and from medial to lateral depending on where their cell bodies sit within the cerebral cortex. The process of wiring up the brain begins prior to birth, with the first axons beginning to form the corpus callosum as early 10-12 weeks of gestation. The corpus callosum grows in size both during gestation and after birth, continuing to connect neurons in each hemisphere, until a fully functioning brain is formed.

Malformations of the corpus callosum usually arise during embryonic and foetal development. There are many developmental processes that must occur in correct sequence for the corpus callosum to form correctly.

First the neurons that will form the corpus callosum must be specified correctly and migrate to their appropriate layer of the cerebral cortex.

Second the neurons must extend an axon that then grows toward its target on the other side of the brain. At the midline of the brain where the axons cross from one hemisphere to another there are specialized glial cells (the other major cell type of the brain) that secrete proteins that guide the axons across the midline.  These proteins are detected by the growing axons of the corpus callosum because they express the specific receptor for the specific proteins they need to detect to navigate their way across the midline.

Another important developmental process at this stage is that the midline between the two hemispheres must fuse together. This step is also mediated by the midline glia. If these glia do not form or do not secrete the correct proteins then the axons of the corpus callosum cannot cross the midline.  Instead, they form large bundles of axons on either side of the midline which are called Probst bundles (because they were discovered by Probst in 1901).

After the callosal axons cross the midline they must grow into their correct target area within the opposite hemisphere and make connections, called synapses, with the dendrites of the neurons in their target area. These circuits become active soon after birth and are refined by activity as the baby begins to interact with its environment and to experience the sights and sounds (and all other sensations) that we take for granted.

Our understanding of how the corpus callosum forms is still in its early stages.  We know that genes and molecules control each of the developmental steps  described above. We know that these similar processes occur in the brains of animals, such as mice, as they form their corpus callosum. Everything we know about the corpus callosum and its development has come from scientific research. Although we understand a lot about how these processes occur we still do not understand much about how the process of midline fusion occurs or how callosal axons find their targets in the contralateral hemisphere. In addition, scientists have identified over 60 genes that are important for formation of the corpus callosum in mice, but we have not yet translated this knowledge into understanding how the corpus callosum forms in human beings. Only a handful of genes have been discovered that regulate corpus callosum formation in humans. Through scientific research we can answer these questions but it takes time and money to conduct the experiments.

Understanding how the corpus callosum forms normally will allow us to understand what goes wrong in agenesis and dysgenesis of the corpus callosum. This work will not only allow us to understand how this fibre tract is formed but may provide some clues as to how the entire brain is wired up during development, since many of the genes and molecules are also used in the formation of other axonal tracts. Unless the brain is wired correctly it cannot function correctly. Since the corpus callosum is such a large fibre tract it is easy
to see by brain scanning or magnetic resonance imaging. A diagnosis of agenesis of the corpus callosum (complete failure of the axons to cross the midline) may indicate either a defect in only the corpus callosum or may be an indication of a more general brain wiring defect. In general, the latter cases are more severe in terms of function.

Surprisingly, even though this is the largest fibre tract in the brain, it is not required for survival.  This is because the corpus callosum does not transmit information about essential life processes such as breathing and heart rate. It is involved in processing information that is primarily processed in the cerebral cortex.

This is the area of the brain that has expanded most throughout evolution, and the corpus callosum evolved as the cerebral cortex expanded.  For example, marsupials and all lower order animals do not have a corpus callosum.  It is only found in placental mammals.

Since the corpus callosum processes cortical information, malformation of the corpus callosum can result in defects in processing this type of information, causing deficits in social interaction, problems with language development, sleep, reading, writing and memory. More severe cases can have deficits in sensory and motor processes, where children don’t learn to walk, or having visual or hearing impairments.  Some people have very few deficits and may not even realize that they were born without a corpus callosum. In these cases it is possible that during brain development, the axons of the corpus callosum found an alternative way to cross the midline, a process included in the concept of brain “plasticity”

Will we ever cure defects in corpus callosum development?  This is difficult to answer since we have so little knowledge about the mechanisms involved in the normal formation of the corpus callosum. As in any other area of medical research, understanding the developmental processes and the genes and molecules that regulate these events, will enable us to identify possible mechanisms of therapies.

Ongoing research in mice is trying to determine if the corpus callosum can be repaired by replacing the affected genes. Another area of research is to develop genetic tests that can be used to identify what gene might be disrupted in patients with corpus callosum defects. Early diagnosis of these gene deficiencies may help doctors and their patients and families to provide a more accurate prognosis for the child and to develop early intervention strategies to help with expected cognitive deficits.