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Dev Cell. 2008 Feb;14(2):227-38. doi: 10.1016/j.devcel.2007.11.001.

piggyBac-based mosaic screen identifies a postmitotic function for cohesin in regulating developmental axon pruning.

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  • 1Howard Hughes Medical Institute, Department of Biological Sciences and Neurosciences Program, Stanford University, Stanford, CA 94305, USA.

Abstract

Developmental axon pruning is widely used to refine neural circuits. We performed a mosaic screen to identify mutations affecting axon pruning of Drosophila mushroom body gamma neurons. We constructed a modified piggyBac vector with improved mutagenicity and generated insertions in >2000 genes. We identified two cohesin subunits (SMC1 and SA) as being essential for axon pruning. The cohesin complex maintains sister-chromatid cohesion during cell division in eukaryotes. However, we show that the pruning phenotype in SMC1(-/-) clones is rescued by expressing SMC1 in neurons, revealing a postmitotic function. SMC1(-/-) clones exhibit reduced levels of the ecdysone receptor EcR-B1, a key regulator of axon pruning. The pruning phenotype is significantly suppressed by overexpressing EcR-B1 and is enhanced by a reduced dose of EcR, supporting a causal relationship. We also demonstrate a postmitotic role for SMC1 in dendrite targeting of olfactory projection neurons. We suggest that cohesin regulates diverse aspects of neuronal morphogenesis.

PMID:
18267091
[PubMed - indexed for MEDLINE]
PMCID:
PMC2268086
Free PMC Article
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