Mechanisms regulating corpus callosum formation, ventricular size, megalencephaly and brain cancer.



Linda J. Richards


The University of Queensland, Queensland Brain Institute, Brisbane, Australia.


Dr. Song-Hai Shi

Time & Location

Time:14:00-15:30 on Tue., Jan. 14, 2019

Location: 143, New Biomedical Museum



Corpus callosum dysgenesis occurs in 1:4000 individuals and can be isolated or associated with a variety of developmental abnormalities. Complete callosal agenesis occurs as a result of interhemispheric remodelling defects which fail to fuse the septal leaves at the midline of the cerebral cortex (Gobius et al., 2016). Interhemispheric remodeling is controlled by the secreted morphogen Fgf8, axonal guidance genes such as deleted in colorectal cancer (Marsh et al., 2017) and the nuclear factor one (NFI) gene family. NFI genes are required for radial progenitors to transition from proliferating stem cells to differentiating neurons and glia, a process essential for interhemispheric remodelling. Mutations in NFI genes cause retention of radial progenitors in a proliferative state which also results in expansion of the ventricular zone (unrelated to hydrocephalus) and megalencephaly in both mice and humans. Similar mechanisms are associated with childhood and adult brain cancers where decreases in NFI expression cause cells to assume a persistent proliferative state, and are unable to differentiate. These results support the hypothesis that defects in the proliferation and differentiation of radial progenitors of the forebrain underlie cortical malformations resulting in an enlarged ventricular surface, megalencephaly and brain wiring defects such as corpus callosum dysgenesis. Similar regulatory mechanisms may also be involved in the aetiology of specific types of brain tumours.