title: Directional neuronal migration is impaired in mice lacking adenomatous polyposis coli 2.
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.
authors.affiliation: Division of Molecular Neurobiology, National Institute for Basic Biology, Okazaki 444-8787, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Shintani
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takeuchi
authors.forename: Akihiro
authors.initials: A
authors.lastname: Fujikawa
authors.forename: Masaharu
authors.initials: M
authors.lastname: Noda
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000172:deficiency / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000235:genetics*; D002478:Cells, Cultured; D002531:Cerebellum / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000172:deficiency* / Q000235:genetics*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000473:pathology*; D011247:Pregnancy
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; C117846:adenomatous polyposis coli protein 2