Summary: A new study reports that without astroglia, the corpus callosum can not form correctly.
Source: Cell Press.
Scientists have identified the cellular origins of the corpus callosum, the 200 million nerve fibers that connect the two hemispheres of the brain. A study of mice and human brains published on October 11 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.
“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 of disorders.”
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.”
Funding: This work was supported by research grants from the Australian National Health and Medical Research Council, the Australian Research Council and the National Institutes of Health, USA and was performed at the Queensland Brain Institute at The University of Queensland, the Departments of Neurology, Psychiatry, Radiology and Biomedical Imaging at the University of California San Francisco, the National Centre for Medical Genetics at Our Lady’s Hospital for Sick Children, and the Center for Integrative Brain Research at the Seattle Children’s Research Institute.
Source: Michaela Kane – Cell Press
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum” by Ilan Gobius, Laura Morcom, Rodrigo Suárez, Jens Bunt, Polina Bukshpun, William Reardon, William B. Dobyns, John L.R. Rubenstein, A. James Barkovich, Elliott H. Sherr, and Linda J. Richards in Cell Reports. Published online October 11 2016 doi:10.1016/j.celrep.2016.09.033
[cbtabs][cbtab title=”MLA”]Cell Press. “Astroglia Zip the Two Halves of the Brain Together.” NeuroscienceNews. NeuroscienceNews, 11 October 2016.
<https://neurosciencenews.com/astroglia-neural-connections-5265/>.[/cbtab][cbtab title=”APA”]Cell Press. (2016, October 11). Astroglia Zip the Two Halves of the Brain Together. NeuroscienceNews. Retrieved October 11, 2016 from https://neurosciencenews.com/astroglia-neural-connections-5265/[/cbtab][cbtab title=”Chicago”]Cell Press. “Astroglia Zip the Two Halves of the Brain Together.” https://neurosciencenews.com/astroglia-neural-connections-5265/ (accessed October 11, 2016).[/cbtab][/cbtabs]
Abstract
Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum
Highlights
•Developmental remodeling of the midline is required for callosal tract formation
•Maturation and intercalation of astroglia mediate interhemispheric remodeling
•Fgf8-Nfi signaling regulates astroglial-mediated interhemispheric remodeling
•Interhemispheric remodeling defects underlie congenital callosal agenesis in humans
Summary
The corpus callosum is the major axon tract that connects and integrates neural activity between the two cerebral hemispheres. Although ∼1:4,000 children are born with developmental absence of the corpus callosum, the primary etiology of this condition remains unknown. Here, we demonstrate that midline crossing of callosal axons is dependent upon the prior remodeling and degradation of the intervening interhemispheric fissure. This remodeling event is initiated by astroglia on either side of the interhemispheric fissure, which intercalate with one another and degrade the intervening leptomeninges. Callosal axons then preferentially extend over these specialized astroglial cells to cross the midline. A key regulatory step in interhemispheric remodeling is the differentiation of these astroglia from radial glia, which is initiated by Fgf8 signaling to downstream Nfi transcription factors. Crucially, our findings from human neuroimaging studies reveal that developmental defects in interhemispheric remodeling are likely to be a primary etiology underlying human callosal agenesis.
“Astroglial-Mediated Remodeling of the Interhemispheric Midline Is Required for the Formation of the Corpus Callosum” by Ilan Gobius, Laura Morcom, Rodrigo Suárez, Jens Bunt, Polina Bukshpun, William Reardon, William B. Dobyns, John L.R. Rubenstein, A. James Barkovich, Elliott H. Sherr, and Linda J. Richards in Cell Reports. Published online October 11 2016 doi:10.1016/j.celrep.2016.09.033
