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Originally published in Science Express on 8 January 2004
Science 13 February 2004:
Vol. 303. no. 5660, pp. 1026 - 1030
DOI: 10.1126/science.1093712
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Reports

Cdh1-APC Controls Axonal Growth and Patterning in the Mammalian Brain

Yoshiyuki Konishi,1 Judith Stegmüller,1 Takahiko Matsuda,2 Shirin Bonni,3 Azad Bonni1*

The anaphase-promoting complex (APC) is highly expressed in postmitotic neurons, but its function in the nervous system was previously unknown. We report that the inhibition of Cdh1-APC in primary neurons specifically enhanced axonal growth. Cdh1 knockdown in cerebellar slice overlay assays and in the developing rat cerebellum in vivo revealed cell-autonomous abnormalities in layer-specific growth of granule neuron axons and parallel fiber patterning. Cdh1 RNA interference in neurons was also found to override the inhibitory influence of myelin on axonal growth. Thus, Cdh1-APC appears to play a role in regulating axonal growth and patterning in the developing brain that may also limit the growth of injured axons in the adult brain.

1 Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA
2 Department of Genetics, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
3 Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive Northwest, Calgary, Alberta T2N 4N1, Canada.

* To whom correspondence should be addressed. E-mail: azad_bonni{at}hms.harvard.edu

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