The role of the microtubule cytoskeleton in neurodevelopmental disorders

Abstract

Neurons depend on the highly dynamic microtubule (MT) cytoskeleton for many different processes during early embryonic development including cell division and migration, intracellular trafficking and signal transduction, as well as proper axon guidance and synapse formation. The coordination and support from MTs is crucial for newly formed neurons to migrate appropriately in order to establish neural connections. Once connections are made, MTs provide structural integrity and support to maintain neural connectivity throughout development. Abnormalities in neural migration and connectivity due to genetic mutations of MT-associated proteins can lead to detrimental developmental defects. Growing evidence suggests that these mutations are associated with many different neurodevelopmental disorders, including intellectual disabilities (ID) and autism spectrum disorders (ASD). In this review article, we highlight the crucial role of the MT cytoskeleton in the context of neurodevelopment and summarize genetic mutations of various MT related proteins that may underlie or contribute to neurodevelopmental disorders.