mSWI/SNF (BAF) Complexes Are Indispensable for the Neurogenesis and Development of Embryonic Olfactory Epithelium.
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.
University Medical Center, Georg-August-University, Goettingen, Germany.
Christina
C
Bachmann
University Medical Center, Georg-August-University, Goettingen, Germany.
Huong
H
Nguyen
University Medical Center, Georg-August-University, Goettingen, Germany.
Joachim
J
Rosenbusch
University Medical Center, Georg-August-University, Goettingen, Germany.
Linh
L
Pham
Max-Planck-Institute for Biophysical Chemistry, Goettingen, Germany.
Tamara
T
Rabe
University Medical Center, Georg-August-University, Goettingen, Germany.
Megha
0000-0002-9229-4944
M
Patwa
University Medical Center, Georg-August-University, Goettingen, Germany.
Godwin
G
Sokpor
Department of Biological Sciences, Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
Rho H
RH
Seong
Sackler Faculty of Medicine, Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Tel Aviv, Israel.
Ruth
R
Ashery-Padan
Max-Planck-Institute for Biophysical Chemistry, Goettingen, Germany.|DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Goettingen, Germany.
Ahmed
A
Mansouri
Max-Planck-Institute for Biophysical Chemistry, Goettingen, Germany.|DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Goettingen, Germany.
Anastassia
A
Stoykova
University Medical Center, Georg-August-University, Goettingen, Germany.|DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Goettingen, Germany.
Jochen F
JF
Staiger
University Medical Center, Georg-August-University, Goettingen, Germany.|DFG Center for Nanoscale Microscopy & Molecular Physiology of the Brain (CNMPB), Goettingen, Germany.
Tran
T
Tuoc
D000818:Animals; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D055495:Neurogenesis; D009831:Olfactory Mucosa / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C491090:Smarcc1 protein, mouse; C587872:Smarcc2 protein, mouse; D014157:Transcription Factors