Adhesive and Cytoskeletal Control of Dendrite Development and Stability

Title Adhesive and Cytoskeletal Control of Dendrite Development and Stability
Lecturer Professor Anthony J. Koleske(Yale University)
Language English
Date&Time 01/08/2015 (Thu) 13:30~14:30
Venue Large seminar room
Proper brain function relies on the extensive synaptic connections that form between neurons. Most excitatory synapses form on small actin-rich protrusions from the sides of dendrites called dendritic spines. Neurons normally have highly-branched dendrites studded with many spines that receive inputs from other neurons. Defects in dendritic spine and dendrite arbor development and stabilization contribute to the pathology of mental retardation, autism, and psychiatric and neurodegenerative diseases. Despite the importance of maintaining neuronal connectivity, the mechanisms that underlie long-term dendritic spine and dendrite stability are poorly understood. Our laboratory has discovered that integrin α3β1 adhesion receptor signaling through Abl2/Arg tyrosine kinase and a set of key downstream targets confers long-term dendritic spine and dendrite arbor stability in the adolescent mouse forebrain. When key upstream components in this pathway (e.g. integrins α3 and β1, Arg) are inactivated, brains mature normally through late adolescence, but exhibit a 25-30% loss of dendritic spines and dendrite arbors by young adulthood, accompanied by deficits in learning, memory, and behavioral flexibility. Importantly, mutations or deletions affecting several pathway components (Arg, p190RhoGAP, SHP-2, integrin β1, GluN2B) are associated with neurodevelopmental and psychiatric disorders in humans. These findings underscore the importance of the mechanisms we have elucidated for human brain circuit stability and function. I will discuss our latest efforts to identify the upstream regulators and downstream targets of this key signaling module and their impact on dendrite and dendritic spine development and stability.

Contact Neuronal Cell Morphogenesis
Naoyuki Inagaki (

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