June 16, 2020
Keio University School of Medicine
Senior Lecturer Yuki Hirota and Professor Kazunori Nakajima of the Department of Anatomy, Keio University School of Medicine, have demonstrated using mice deficient in the VLDLR receptor that the molecule Reelin—which controls brain formation and has been implicated in various neuropsychiatric disorders—correctly positions neurons by acting on their VLDLR receptors to stop them at the appropriate location during brain formation.
Brain function is supported by networks formed by numerous neurons. For these networks to be formed correctly, it is crucial that neurons are positioned appropriately during brain formation. Neurons are born deep within the brain and migrate toward the brain's surface. However, in mice lacking Reelin, normal cell migration does not occur, and abnormalities in this molecule are known to be associated with neuropsychiatric disorders in humans. The function of Reelin is thought to involve both "aggregation" (moving and gathering neurons to specific locations) and "termination" (stopping them at the appropriate place). In a previous study, our research group reported that Reelin acts on the ApoER2 receptor on neurons to cause migrating neurons to aggregate. This time, we have shown that Reelin stops this migration at the appropriate position via another receptor on neurons, VLDLR. We have clarified that Reelin performs two types of control, "aggregation" and "termination," by acting on different receptors during multiple stages of neuronal migration.
In recent years, attention has been drawn to the possibility that subtle defects, such as abnormalities in neuronal positioning during brain formation, may underlie various neuropsychiatric disorders. These findings are expected to contribute to the future elucidation of the pathology of these disorders and the development of therapeutic methods.
The results of this research were published in the online edition of the journal "Development" on June 15, 2020 (UK time). It will also be featured in the "Research Highlight" article of the issue.
Please see below for the full press release.