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Published Online January 8, 2004
Science DOI: 10.1126/science.1093712

Reports

Submitted on November 17, 2003
Accepted on December 22, 2003

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

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

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, USA.
3 Department of Biochemistry and Molecular Biology, University of Calgary, 3330 Hospital Drive N.W. Calgary, Alberta, Canada.

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

The anaphase promoting complex (APC) is highly expressed in postmitotic neurons, but its function in the nervous system remained 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 RNAi 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.


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