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mSWI/SNF(BAF)复合物对于胚胎嗅觉上皮的神经发生和发育不可或缺。

mSWI/SNF (BAF) Complexes Are Indispensable for the Neurogenesis and Development of Embryonic Olfactory Epithelium.

作者信息

Bachmann Christina, Nguyen Huong, Rosenbusch Joachim, Pham Linh, Rabe Tamara, Patwa Megha, Sokpor Godwin, Seong Rho H, Ashery-Padan Ruth, Mansouri Ahmed, Stoykova Anastassia, Staiger Jochen F, Tuoc Tran

机构信息

University Medical Center, Georg-August-University, Goettingen, Germany.

Max-Planck-Institute for Biophysical Chemistry, Goettingen, Germany.

出版信息

PLoS Genet. 2016 Sep 9;12(9):e1006274. doi: 10.1371/journal.pgen.1006274. eCollection 2016 Sep.

Abstract

Neurogenesis is a key developmental event through which neurons are generated from neural stem/progenitor cells. Chromatin remodeling BAF (mSWI/SNF) complexes have been reported to play essential roles in the neurogenesis of the central nervous system. However, whether BAF complexes are required for neuron generation in the olfactory system is unknown. Here, we identified onscBAF and ornBAF complexes, which are specifically present in olfactory neural stem cells (oNSCs) and olfactory receptor neurons (ORNs), respectively. We demonstrated that BAF155 subunit is highly expressed in both oNSCs and ORNs, whereas high expression of BAF170 subunit is observed only in ORNs. We report that conditional deletion of BAF155, a core subunit in both onscBAF and ornBAF complexes, causes impaired proliferation of oNSCs as well as defective maturation and axonogenesis of ORNs in the developing olfactory epithelium (OE), while the high expression of BAF170 is important for maturation of ORNs. Interestingly, in the absence of BAF complexes in BAF155/BAF170 double-conditional knockout mice (dcKO), OE is not specified. Mechanistically, BAF complex is required for normal activation of Pax6-dependent transcriptional activity in stem cells/progenitors of the OE. Our findings unveil a novel mechanism mediated by the mSWI/SNF complex in OE neurogenesis and development.

摘要

神经发生是一个关键的发育事件,在此过程中神经元由神经干/祖细胞产生。据报道,染色质重塑BAF(mSWI/SNF)复合物在中枢神经系统的神经发生中起重要作用。然而,BAF复合物在嗅觉系统中神经元生成是否必需尚不清楚。在这里,我们鉴定了onscBAF和ornBAF复合物,它们分别特异性存在于嗅觉神经干细胞(oNSC)和嗅觉受体神经元(ORN)中。我们证明BAF155亚基在oNSC和ORN中均高表达,而BAF170亚基仅在ORN中高表达。我们报告说,条件性缺失BAF155(onscBAF和ornBAF复合物中的核心亚基)会导致发育中的嗅觉上皮(OE)中oNSC的增殖受损以及ORN的成熟和轴突发生缺陷,而BAF170的高表达对ORN的成熟很重要。有趣的是,在BAF155/BAF170双条件敲除小鼠(dcKO)中缺乏BAF复合物时,OE未分化。从机制上讲,BAF复合物是OE干细胞/祖细胞中Pax6依赖性转录活性正常激活所必需的。我们的发现揭示了mSWI/SNF复合物在OE神经发生和发育中介导的一种新机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d8f1/5017785/1367e5adeb40/pgen.1006274.g001.jpg

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