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

        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, Public Library of Science 2016 PLoS genetics Vol.12 No.9

        <▼1><P>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.</P></▼1><▼2><P><B>Author Summary</B></P><P>The stepwise differentiation of oNSCs to immature and mature ORNs is driven by a defined set of transcription factors. Yet, how these transcription factors act in concert with epigenetic and chromatin-remodeling cofactors to orchestrate OE neurogenesis is unknown. In this study, we identified subunits of chromatin-remodeling mSWI/SNF (BAF) complexes in oNSCs and ORNs. Our results indicate that early formation of the OE depends on the presence of BAF complexes. Our study highlights BAF155 and BAF170 as key factors that control specification, self-renewal of oNSCs and neuronal maturation in the developing OE. Furthermore, we uncover a novel mechanism in which the interaction between BAF155-containing BAF complexes with the transcription factor Pax6 determines OE neurogenesis.</P></▼2>

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