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染色质重塑因子 Bap55 通过 TIP60 复合物发挥作用,调节嗅觉投射神经元树突靶向。

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

机构信息

Howard Hughes Medical Institute, Department of Biology, Stanford University, Stanford, CA 94305, USA.

出版信息

Neural Dev. 2011 Feb 1;6:5. doi: 10.1186/1749-8104-6-5.

Abstract

BACKGROUND

The Drosophila olfactory system exhibits very precise and stereotyped wiring that is specified predominantly by genetic programming. Dendrites of olfactory projection neurons (PNs) pattern the developing antennal lobe before olfactory receptor neuron axon arrival, indicating an intrinsic wiring mechanism for PN dendrites. These wiring decisions are likely determined through a transcriptional program.

RESULTS

We find that loss of Brahma associated protein 55 kD (Bap55) results in a highly specific PN mistargeting phenotype. In Bap55 mutants, PNs that normally target to the DL1 glomerulus mistarget to the DA4l glomerulus with 100% penetrance. Loss of Bap55 also causes derepression of a GAL4 whose expression is normally restricted to a small subset of PNs. Bap55 is a member of both the Brahma (BRM) and the Tat interactive protein 60 kD (TIP60) ATP-dependent chromatin remodeling complexes. The Bap55 mutant phenotype is partially recapitulated by Domino and Enhancer of Polycomb mutants, members of the TIP60 complex. However, distinct phenotypes are seen in Brahma and Snf5-related 1 mutants, members of the BRM complex. The Bap55 mutant phenotype can be rescued by postmitotic expression of Bap55, or its human homologs BAF53a and BAF53b.

CONCLUSIONS

Our results suggest that Bap55 functions through the TIP60 chromatin remodeling complex to regulate dendrite wiring specificity in PNs. The specificity of the mutant phenotypes suggests a position for the TIP60 complex at the top of a regulatory hierarchy that orchestrates dendrite targeting decisions.

摘要

背景

果蝇嗅觉系统表现出非常精确和刻板的连接,主要由遗传编程决定。嗅觉投射神经元(PNs)的树突在嗅觉受体神经元轴突到达之前就对发育中的触角叶进行了模式化,这表明了 PNs 树突的内在连接机制。这些连接决策可能是通过转录程序决定的。

结果

我们发现,Brahma 相关蛋白 55kD(Bap55)的缺失会导致 PNs 高度特异性的靶向错误表型。在 Bap55 突变体中,原本靶向 DL1 神经球的 PNs 以 100%的外显率靶向 DA4l 神经球。Bap55 的缺失还导致了一个 GAL4 的去抑制,该 GAL4 的表达通常局限于一小部分 PNs。Bap55 是 Brahma(BRM)和 Tat 相互作用蛋白 60kD(TIP60)ATP 依赖性染色质重塑复合物的成员。Bap55 突变体的表型部分被 Domino 和 Enhancer of Polycomb 突变体,TIP60 复合物的成员所 recapitulate。然而,在 Brahma 和 Snf5-related 1 突变体中,BRM 复合物的成员,却出现了不同的表型。Bap55 突变体的表型可以通过 Bap55 的后期表达,或其人类同源物 BAF53a 和 BAF53b 来挽救。

结论

我们的结果表明,Bap55 通过 TIP60 染色质重塑复合物发挥作用,调节 PNs 中树突连接的特异性。突变体表型的特异性表明 TIP60 复合物在调控树突靶向决策的调控层次结构的顶端发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/31f9/3038883/de708625ce2d/1749-8104-6-5-1.jpg

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