Cellular and Molecular Biology

Friday 19/1/2024 h. 9.00 am - Webinar

Makoto Sato, Department of Anatomy and Neuroscience, Graduate School of Medicine; Division of Child Development, United Graduate School of Child Development (UGSCD) - Osaka University, JAPAN

Cytoskeletons and cortical development: How does the neocortex develop to establish the prototype of neuronal circuits by neuronal migration and collateral formation?

To understand the complex neuronal circuits for higher functioning of the neocortex from a compositional perspective, I have studied cortical development, in particular cytoskeletal regulatory mechanisms underlying migration and collateral formation. Periventricular nodular heterotopia gave me the first hint to study cortical development focusing on the regulation of cytoskeletons. Periventricular heterotopia is a hereditary disease in which the brain has a second cortex (cluster of nerve cells) around the ventricle, a so-called double cortex, and one of its characteristics is intractable epilepsy.

The cause of the disease is believed to be a mutation in the actin-binding protein filamin A on the X chromosome, suggesting that filamin A is important for neurons to migrate out of the cortical ventricular zone to form the neocortex. We have identified and studied a novel molecule, FILIP (filamin A interacting protein), which promotes the degradation of filamin A. Very recently, it was reported that mutations in FILIP (FILIP1 in human) cause congenital arthrogryposis multiplex, intellectual disability, holoprosencephaly, and encephalocele in human (FILIP disease). In my talk, I will introduce a series of FILIP-related studies to and its regulatory factors, including some unpublished data.

It is generally believed that mutation of molecules involved in neuronal migration increases susceptibility to various neuropsychiatric diseases, but the relationship between these mutations has not been fully elucidated. Therefore, to examine changes in neural networks due to variations in neuronal arrangement, we first constructed a system to visualize single-cell level neural networks for individual cerebral cortical neurons. Sequential collateral formation to apparently predetermined targets is critical to establish the prototype of neuronal circuits. I will also present our latest results that underlie such collateral formation in my talk.

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