The chromatin remodeling factor Bap55 functions through the TIP60 complex to regulate olfactory projection neuron...

Area of Science:

• Neuroscience
• Genetics
• Developmental Biology

Background:

• The Drosophila olfactory system displays precise, genetically programmed wiring.
• Olfactory projection neuron (PN) dendrites establish antennal lobe patterns before axon arrival, suggesting intrinsic wiring mechanisms.
• Transcriptional programs likely govern these PN dendrite wiring decisions.

Purpose of the Study:

• To investigate the role of Brahma associated protein 55 kD (Bap55) in Drosophila olfactory projection neuron dendrite targeting.
• To elucidate the molecular mechanisms underlying the genetic programming of olfactory system wiring.

Main Methods:

• Analysis of Bap55 mutant Drosophila for olfactory projection neuron (PN) mistargeting phenotypes.
• Examination of GAL4 expression patterns in Bap55 mutants.
• Assessment of Bap55's association with Brahma (BRM) and Tat interactive protein 60 kD (TIP60) chromatin remodeling complexes.
• Complementation tests with mutants in BRM and TIP60 complex members.
• Rescue experiments using postmitotic expression of Bap55 and its human homologs.

Main Results:

• Loss of Bap55 results in 100% penetrant mistargeting of PNs from the DL1 to the DA4l glomerulus.
• Bap55 mutation leads to derepression of a specific GAL4 line.
• Bap55 is part of both BRM and TIP60 chromatin remodeling complexes.
• Mutants of TIP60 complex members (Domino, Enhancer of Polycomb) partially recapitulate the Bap55 phenotype, while BRM complex mutants (Brahma, Snf5-related 1) show distinct phenotypes.
• Postmitotic expression of Bap55 or its human homologs rescues the PN mistargeting phenotype.

Conclusions:

• Bap55 functions through the TIP60 chromatin remodeling complex to ensure dendrite wiring specificity in Drosophila PNs.
• The specific Bap55 mutant phenotype suggests the TIP60 complex plays a critical role at the top of the regulatory hierarchy controlling dendrite targeting.