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Mosaic Analysis of Gene Function in Postnatal Mouse Brain Development by Using Virus-based Cre Recombination
Published on: August 1, 2011
piggyBac-based mosaic screen identifies a postmitotic function for cohesin in regulating developmental axon pruning.
Oren Schuldiner1, Daniela Berdnik, Jonathan Ma Levy
1Howard Hughes Medical Institute, Department of Biological Sciences and Neurosciences Program, Stanford University, Stanford, CA 94305, USA.
Developmental Cell
|February 13, 2008
Summary
Cohesin subunits SMC1 and SA are essential for developmental axon pruning in Drosophila neurons. This study reveals a postmitotic function for cohesin in neuronal development and circuit refinement.
Area of Science:
- Neuroscience
- Developmental Biology
- Genetics
Background:
- Developmental axon pruning is crucial for refining neural circuits.
- The cohesin complex is known for its role in sister-chromatid cohesion during cell division.
Purpose of the Study:
- To identify genes involved in Drosophila mushroom body gamma neuron axon pruning using a mosaic screen.
- To investigate the function of cohesin subunits in postmitotic neuronal development.
Main Methods:
- Mosaic genetic screen using a modified piggyBac vector for mutagenesis.
- Analysis of axon pruning defects in cohesin subunit mutants (SMC1, SA).
- Rescue experiments involving neuronal expression of SMC1 and manipulation of ecdysone receptor (EcR-B1) levels.
Main Results:
- Mutations in cohesin subunits SMC1 and SA impair axon pruning.
- The pruning defect in SMC1 mutants is neuronal and postmitotic.
- Reduced SMC1 levels lead to decreased ecdysone receptor EcR-B1, impacting pruning.
- SMC1 also plays a postmitotic role in dendrite targeting.
Conclusions:
- Cohesin subunits SMC1 and SA are essential for developmental axon pruning.
- Cohesin has a critical postmitotic function in neuronal morphogenesis, including axon pruning and dendrite targeting.
- Cohesin's role extends beyond cell division to regulate key aspects of neural circuit refinement.
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