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

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.

MeSH terms

  • Animals
  • Cells, Cultured
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism
  • DNA-Binding Proteins
  • Gene Deletion
  • Mice
  • Mice, Inbred C57BL
  • Neurogenesis*
  • Olfactory Mucosa / cytology
  • Olfactory Mucosa / embryology
  • Olfactory Mucosa / metabolism*
  • Olfactory Receptor Neurons / cytology
  • Olfactory Receptor Neurons / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Smarcc1 protein, mouse
  • Smarcc2 protein, mouse
  • Transcription Factors

Grants and funding

This work was supported by the Research Program at the Faculty of Medicine, Georg-August University Göttingen (to TT), DFG grants (TU432/1-1 and TU432/3-1 to TT), Vietnamese Government Scholarship (HN) and DFG-CNMPB (to TT, JFS, AM and AS). The authors also acknowledge support from the Open Access Publication Funds of the Göttingen University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.