RT Journal Article
SR Electronic
T1 Directional Neuronal Migration Is Impaired in Mice Lacking Adenomatous Polyposis Coli 2
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6468
OP 6484
DO 10.1523/JNEUROSCI.0590-12.2012
VO 32
IS 19
A1 Shintani, Takafumi
A1 Takeuchi, Yasushi
A1 Fujikawa, Akihiro
A1 Noda, Masaharu
YR 2012
UL http://www.jneurosci.org/content/32/19/6468.abstract
AB 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.