Topic
Precise regulation of microtubules in developing neurons is essential for healthy brain development. Dysregulation of microtubules has been shown to alter neuronal migration, axon and dendrite growth and guidance, and organelle transport, and is associated with several neurodevelopmental disorders such as autism spectrum disorder (ASD), epilepsy, and schizophrenia. Although the mechanisms that control microtubules in neurons remain poorly understood, microtubule-associated proteins play a key role. Using single-molecule in vitro systems, neuronal cultures, and newly generated mouse models, we demonstrate that impaired microtubule polymerization due to deficiency in a specific isoform of microtubule associated protein CRMP2 leads to defects in axon growth and guidance, synapse refinement, and sociability behavior in mice associated with ASD. Additionally, we show that disrupted microtubule-based mitochondrial transport, caused by alterations in mitochondrial adaptor proteins, results in abnormal neuronal migration, impaired cortical development, and severe epileptic encephalopathies. Our work reveals novel mechanisms by which microtubule‑associated proteins control brain development and drive the pathogenesis of neurodevelopmental disorders in vivo.
About Dr. Balastik
Dr. Balastik earned his Ph.D. in Neuroscience from the International Max Planck Research School for Neurosciences at the University of Göttingen, Germany, under Prof. Peter Gruss. In 2004, he moved to Boston to undertake postdoctoral training at Harvard Medical School (BIDMC) in the laboratory of Prof. Kun Ping Lu. In 2012, he joined the Institute of Molecular Genetics at the Czech Academy of Sciences in Prague as a principal investigator, and in 2014 he established and became Head of the Laboratory of Molecular Neurobiology at the Institute of Physiology, Czech Academy of Sciences.