piggyBac-based mosaic screen identifies a postmitotic function for cohesin in regulating developmental axon pruning.
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.
Schuldiner
Oren
O
Howard Hughes Medical Institute, Department of Biological Sciences and Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
Berdnik
Daniela
D
Levy
Jonathan Ma
JM
Wu
Joy S
JS
Luginbuhl
David
D
Gontang
Allison Camille
AC
Luo
Liqun
L
D000483:Alleles; D000818:Animals; D001369:Axons / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004251:DNA Transposable Elements / Q000235:genetics*; D003712:Dendrites / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology* / Q000254:growth & development*; D005819:Genetic Markers; D008938:Mitosis; D009030:Mosaicism; D024521:Mushroom Bodies / Q000166:cytology; D016254:Mutagenesis, Insertional; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000378:metabolism*; D009833:Olfactory Pathways / Q000378:metabolism; D010641:Phenotype; D011987:Receptors, Steroid / Q000378:metabolism; D019076:Transgenes; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004251:DNA Transposable Elements; D029721:Drosophila Proteins; D005819:Genetic Markers; D009687:Nuclear Proteins; D011987:Receptors, Steroid; D000097722:Cohesins; D000098550:Structural Maintenance of Chromosome Protein 1; C114087:SA protein, Drosophila; C055469:ecdysone receptor