The lab observed that astrocytes are initially located beneath the area filled with fibroblasts, however, 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. Results show that this column of astroglia acts as a bridge for callosal axons and allows them to cross between the two sides of the brain. Data findings show that 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 group state that when there was an issue with molecular signaling, the astroglial cells didn’t change into multipolar cells, which prevents the formation of the callosal tract and resulted in callosal agenesis.  The researchers explain that this midline area is one of the first places in the brain that exhibit these astroglial cell changes, and if these cells don’t make this transition, the remodeling process to form the corpus callosum doesn’t get started.  They conclude that they’ve finally discovered one of the major causes for this group of disorders.

The team surmise that their findings show how astroglia remodel the telencephalic interhemispheric fissure during mouse and human development.  They go on to add that further evidence demonstrates that defects in interhemispheric remodeling underlie callosal agenesis in mice and humans.  For the future, the researchers state they now plan to use this knowledge to help make better diagnostic tests for callosal agenesis.

Source: Queensland Brain Institute at The University of Queensland

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. Richards et al 2016.