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Centrosome-mediated microtubule remodeling during axon formation in human iPSC-derived neurons

ABSTRACT: Local microtubule remodeling is critical for axon formation, the first step in establishing neuronal polarity. However, the function of the microtubule organizing centrosomes during the onset of axon formation, is still under debate. Here, we demonstrate that centrosomes play an essential role in controlling axon formation in human induced pluripotent stem cell (iPSC)-derived neurons. Depleting centrioles, the core components of centrosomes, in unpolarized human neuronal stem cells results in various axon developmental defects at later stages, including immature action potential firing, mistargeting of microtubule associated protein Trim46, suppressed expression of growth cone proteins and affected growth cone morphologies. Live-cell imaging of dynamic microtubules reveals that centriole loss prevents axonal microtubule reorganization towards the unique parallel plus-end out microtubule bundles in growing axons. We propose that centrosomes mediate microtubule remodeling during axon specification in human iPSC-derived neurons, thereby setting the foundation for further axon development and function.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stem Cell, Cell Culture

DISEASE(S): Disease Free

SUBMITTER: Robbelien Kooistra

LAB HEAD: Casper Hoogenraad

PROVIDER: PXD020221 | Pride | 2021-02-12

REPOSITORIES: Pride

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