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

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

doi:10.1371/journal.pgen.1006274

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.

Highlights

Olfaction—the sense of smell—influences many primitive behaviors, including feeding, reproduction, social interactions, and fear responses [1,2,3]
Using a conditional deletion approach in the mouse in which BAF155 and BAF170 deficiency is restricted to Foxg1-positive cells, we examined the phenotypes of single mutants (BAF155cKO, BAF170cKO) and double-conditional knockout mice (dcKO) mutants for BAF155 and BAF170, subunits in both onscBAF and ornBAF complexes, during development of the olfactory epithelium (OE)
We examined whether such a subunit switch takes place during differentiation from olfactory neural stem cells (oNSCs) to olfactory receptor neurons (ORNs)

Summary

Introduction

Olfaction—the sense of smell—influences many primitive behaviors, including feeding, reproduction, social interactions, and fear responses [1,2,3]. The mouse OE arises from olfactory placodes (OPs) during early embryogenesis [1,2,3]. Whereas neurogenesis is initiated very early in development, the majority of olfactory epithelial cells are proliferating olfactory neural stem cells (oNSCs) until E11.5 (S1A and S1B Fig) [4,5]. The majority of apical cells are proliferative glial-like sustentacular (SUS) cells, whereas basal cells are precursors of olfactory receptor neurons (ORNs), called olfactory sensory neurons (OSNs) [1,2,6,7]. Among non-neuronal–lineage cells of the OE, SUS cells are thought to arise from oNSCs, but details of this process are still under investigation (S1A and S1C Fig) [10]

Methods

Results

Conclusion