HOW DO THE CYTOSKELETON AND ITS BINDING PARTNERS CONTRIBUTE TO THE ESTABLISHMENT OF THE BRAIN MORPHOLOGY AND ITS FUNCTION?

With the ultimate goal of elucidating the brain mechanisms underlying intelligence, I have been tackling this question by investigating the mechanisms that underlie the formation of brain structures during development. Cell migration and completion of neurotransmission are crucial events that support the development. Because the cytoskeleton is essential for these processes, I have been studying these themes from a cytoskeletal perspective. Periventricular nodular heterotopia is a genetic disorder characterized by the presence of a second cortex (a cluster of neurons) around the ventricles, known as a double cortex. One of the characteristics of this disorder is intractable epilepsy. This disease is believed to be caused by mutations in the actin-binding protein filamin A, which is located on the X chromosome. It has been suggested that filamin A plays a crucial role in cell migration from the ventricular region during cortical development. We have identified and are currently studying a novel molecule, FILIP (filamin A-interacting protein), which promotes the degradation of filamin A. Recently, mutations in FILIP (FILIP1 in humans) have been reported to cause arthrogryposis multiplex congenita, intellectual disability, and encephalocele in humans (FILIP1 disease). At first, I will introduce our research on FILIP and its regulatory factors. Next, we will present our data on how other cytoskeletal molecules contribute to brain development and maturation. On the other hand, when we look at neural circuits, we notice that function and circuit formation are intricately intertwined to enable the brain to function. From this perspective, we have also taken an approach to unravel cells and their associated circuits that are specific to higher animals. We will cite examples of such research and introduce our current approach.