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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Axons / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Cell Proliferation
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Transposable Elements / genetics*
  • Dendrites / metabolism
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / growth & development*
  • Genetic Markers
  • Mitosis*
  • Mosaicism*
  • Mushroom Bodies / cytology
  • Mutagenesis, Insertional
  • Mutation / genetics
  • Nuclear Proteins / metabolism*
  • Olfactory Pathways / metabolism
  • Phenotype
  • Receptors, Steroid / metabolism
  • Transgenes

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA Transposable Elements
  • Drosophila Proteins
  • Genetic Markers
  • Nuclear Proteins
  • Receptors, Steroid
  • SA protein, Drosophila
  • cohesins
  • ecdysone receptor
  • structural maintenance of chromosome protein 1