Cdh1-APC controls axonal growth and patterning in the mammalian brain.
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.
Konishi
Yoshiyuki
Y
Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Stegmüller
Judith
J
Matsuda
Takahiko
T
Bonni
Shirin
S
Bonni
Azad
A
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002525:Cerebellar Cortex / Q000166:cytology* / Q000254:growth & development; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D018274:Electroporation; D009024:Morphogenesis; D009154:Mutation; D009186:Myelin Sheath / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D034622:RNA Interference; D051381:Rats; D020318:Rats, Long-Evans; D014162:Transfection; D043743:Ubiquitin-Protein Ligase Complexes / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; C498962:Fbxo5 protein, rat; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome