Directional neuronal migration is impaired in mice lacking adenomatous polyposis coli 2.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Takafumi ShintaniMasaharu Noda

Abstract

Adenomatous polyposis coli 2 (APC2) is a family member of APC and mainly expressed in the nervous system. We previously reported that APC2 plays a critical role in axonal projection through the regulation of microtubule stability. Here, we show that a lack of Apc2 induces severe laminary defects in some regions of the mouse brain, including the cerebral cortex and cerebellum. In vivo BrdU labeling and immunohistochemical analyses with specific markers revealed that the laminary abnormalities are a result of dysregulated neuronal migration by a cell-autonomous mechanism. Using total internal reflection fluorescent microscopy, we found that APC2 is distributed along actin fibers as well as microtubules. Cerebellar granule cells in dissociated cultures and in vivo showed that BDNF-stimulated directional migration is impaired in Apc2-deficient neurons. We revealed that this impairment stems from the dysregulations of Rho family GTPase activation and TrkB localization, which disrupts the formation of BDNF-stimulated F-actin at the leading edge. Thus, APC2 is an essential mediator of the cytoskeletal regulation at leading edges in response to extracellular signals.

Citations

Feb 8, 2014·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Allison PiovesanPierluigi Strippoli
Feb 6, 2013·The Journal of Cell Biology·Yasuhisa SakamotoSandrine Etienne-Manneville
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Jun 4, 2015·Translational Psychiatry·X ZhengE Feingold
Mar 11, 2015·Cell Reports·Mariam AlmuriekhiMasaharu Noda
May 31, 2016·Molecular Cytogenetics·Pietro PalumboMassimo Carella
Jul 12, 2019·BMC Cancer·Noha-Ehssan MohamedAlan R Clarke
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Feb 16, 2019·Proceedings of the National Academy of Sciences of the United States of America·Haihong YangHaitao Wu

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Adenomatous polyposis coli is a protein encoded by the APC gene and acts as a tumor suppressor. Discover the latest research on adenomatous polyposis coli here.