QBI Neuroscience Seminar: “Understanding the molecular origins of cortical malformations'
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- Professor Helen Cooper
Queensland Brain Institute
University of Queensland
Title: 'Understanding the molecular origins of cortical malformations'
Abstract: The fidelity of neocortical development is dependent on the highly polarized morphology of the neuroepithelial progenitors (NEPs) - the neural stem cells that line the embryonic ventricles. During embryogenesis the neuroepithelium resists the mechanical stresses exerted by dynamic tissue movements through the assembly of cadherin-based cell-cell junctions which are stabilized by the underlying actin cytoskeleton. Failure to establish the cadherin-actin link results in loss of NEP structure and function, thereby giving rise to neural tube defects and cortical malformations. I will describe an unexpected function for the Neogenin axon guidance receptor in maintaining NEP junctional stability by anchoring the actin polymerization machinery (WAVE Regulatory Complex and Arp2/3) to the cadherin adhesion complex. We further show that disrupting Neogenin function in NEPs leads to cortical malformations and hydrocephalus. Our latest studies indicate that a similar mechanism may underpin spine formation and synaptic plasticity.
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