Luana Soares, Francis Szele and colleagues from Oncology (Eric O’Neill), from Paediatrics (Mathew Wood) and from DPAG (Zoltan Molnar, Mootaz Salman), have identified Galectin-3 as a key regulator of neural development, establishing its contribution to brain growth.
Lead author Luana Soares explained this is the first time that Galectin-3, previously recognized for its role in establishing apical-basal polarity in epithelial cells, has been identified in human neural progenitors, where it plays a vital role in maintaining cellular junctions. She noted that this process is tightly regulated during brain development, and when disrupted, can contribute to neurodevelopmental problems. They blocked Gal-3 genetically and pharmacologically and this caused cortical stem cells to shift their modes of division. Zoltán Molnár noted that the findings demonstrate the power of mouse models for detecting mechanisms for cortical neurogenesis and migration disorders despite considerable differences in the composition and proportions of cortical progenitors and modes of migrations in human brain. The validation of expression patterns in human and the functional tests advise caution that these mechanisms are could be involved in human cortical developmental disorders.
Francis Szele stated that excessive inflammation in the developing brain can be a risk factor for diseases such as schizophrenia and autism. Therefore the role of Gal-3 in inflammation in the developing brain is an important topic. He and others in the field have shown that Gal-3 is massively upregulated in brain injury and disease, and alters signalling pathways and neuropathology. Surprisingly this study suggests that not increasing but decreasing Gal-3 can lead to malformations and that healthy brain growth in humans. He also cautions that one of the compounds they used to decrease Gal-3 function MCP is available over-the-counter but may be harmful to developing fetuses.
Read the paper as published in Science Advances here