A Morphometric Screen Identifies Specific Roles for Microtubule-Regulating Genes in Neuronal Development of P19 Stem Cells |
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Authors: | Julia Arens Thanh-Thuy Duong Leif Dehmelt |
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Affiliation: | Department of Systemic Cell Biology, Max Planck Institute of Molekular Physiology, and Fachbereich Chemische Biologie, Dortmund University of Technology, Dortmund, Germany.; Stanford University School of Medicine, United States of America, |
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Abstract: | The first morphological change after neuronal differentiation is the microtubule-dependent initiation of thin cell protrusions called neurites. Here we performed a siRNA-based morphometric screen in P19 stem cells to evaluate the role of 408 microtubule-regulating genes during this early neuromorphogenesis step. This screen uncovered several novel regulatory factors, including specific complex subunits of the microtubule motor dynein involved in neurite initiation and a novel role for the microtubule end-binding protein EB2 in attenuation of neurite outgrowth. Epistasis analysis suggests that competition between EB1 and EB2 regulates neurite length, which links its expression to neurite outgrowth. We propose a model that explains how microtubule regulators can mediate cellular morphogenesis during the early steps of neuronal development by controlling microtubule stabilization and organizing dynein-generated forces. |
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