The 200 million nerve fibers that connect the two hemispheres
of the brain is known as corpus callosum. Scientists have identified the cellular origins of the corpus
A study of mice and human brains published in Cell Reports
shows that during development, astroglia, the
main supporting cells of the brain, weave themselves between the right
and left lobes, and form the bridge for axons to grow across the gap.
Without these astroglia, the corpus callosum doesn't form correctly,
causing a condition called callosal agenesis - which affects 1 out of
4,000 people - and a range of developmental disorders.
‘During development, astroglia weave themselves between the right and left lobes, and form the bridge for axons to grow across the gap.’
"Very little is known about the cause of callosal agenesis, and
there hasn't been a satisfactory explanation for how it occurs," says
first author Ilan Gobius, a postdoctoral research fellow at the
Queensland Brain Institute, University of Queensland in Australia. "We
believe we've finally discovered one of the major causes for this group
During development, the hemispheres of the brain are separated by a
gap filled with fibroblasts - and other non-neural cells. In order to see
how callosal axons navigated around this area to connect the
hemispheres, the researchers used mice embryos to observe the growth of
individual axons. They observed that the axons cannot grow through this
gap, and instead grow down and around it to connect the two hemispheres
of the brain. However, they don't do this on their own; instead they
rely on astroglial cells to guide their path.
Using the mice embryos and human brain scans, the team lead by Linda
Richards, Deputy Director of the Queensland Brain Initiative found that
these astroglial cells are initially located beneath the area filled
with fibroblasts, but during fetal development a molecular pathway
signals the astroglia to migrate forward and mature, allowing them to
weave together into a thick column along the center of the brain, which
pushes back against the gap and causes it to shrink.
This column of
astroglia acts as a bridge for callosal axons and allows them to cross
between the two sides of the brain. As this bridge grows, the gap
between the hemispheres shrinks until only a small portion of it
remains, and the corpus callosum begins to form.
The researchers saw that when there was an issue with molecular
signaling, the astroglial cells didn't change into multipolar cells.
This prevented the formation of the callosal tract and resulted in
callosal agenesis. "This midline area is one of the first places in the
brain that you normally start to see these astroglial cell changes,"
says Gobius. "And we found that if these cells don't make this
transition, the remodeling process that you need to form the corpus
callosum doesn't get started."
Moving forward, the team hopes to use this knowledge to help make
better diagnostic tests for callosal agenesis. As of now, doctors can
only diagnose the disorder during fetal development using an ultrasound
or MRI, but since the condition can range in severity, the lack of an
accurate genetic test makes it difficult to council parents about what
developmental issues to expect in their child.
"The field is desperate for a genetic test for this disorder," says
Richards. "This opens up the possibility for testing for genes like
those that Dr. Gobius identified. Identifying the cellular process that
causes this range of disorders is very important for looking to the
future and finding new genes for possible therapeutic targets."