Publication: Commensal Bacteria Regulate Gene Expression and Differentiation in Vertebrate Olfactory Systems Through Transcription Factor REST
Authors
Casadei, Elisa ; Tacchi, Luca ; Lickwar, Colin R. ; Espenschied, Scott T. ; Davison, James M. ; Muñoz, Pilar ; Rawls, John F. ; Salinas, Irene
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Publisher
Oxford University Press
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DOI
https://doi.org/10.1093/chemse/bjz050
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info:eu-repo/semantics/article
Description
© 2019. The authors. This document is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0
This document is the accepted version of a published work that appeared in final form in Chemical Senses.
To access the final work, see DOI: https://doi.org/10.1093/chemse/bjz050
Abstract
Sensory systems such as the olfactory system detect chemical stimuli and thereby determine the relationships
between the animal and its surroundings. Olfaction is one of the most conserved and ancient
sensory systems in vertebrates. The vertebrate olfactory epithelium is colonized by complex microbial
communities, but microbial contribution to host olfactory gene expression remains unknown. In this
study, we show that colonization of germ-free zebrafish and mice with microbiota leads to widespread
transcriptional responses in olfactory organs as measured in bulk tissue transcriptomics and RT-qPCR.
Germ-free zebrafish olfactory epithelium showed defects in pseudostratification; however, the size of
the olfactory pit and the length of the cilia were not different from that of colonized zebrafish. One of
the mechanisms by which microbiota control host transcriptional programs is by differential expression
and activity of specific transcription factors (TFs). REST (RE1 silencing transcription factor, also
called NRSF) is a zinc finger TF that binds to the conserved motif repressor element 1 found in the promoter
regions of many neuronal genes with functions in neuronal development and differentiation.
Colonized zebrafish and mice showed increased nasal expression of REST, and genes with reduced
expression in colonized animals were strongly enriched in REST-binding motifs. Nasal commensal
bacteria promoted in vitro differentiation of Odora cells by regulating the kinetics of REST expression.
REST knockdown resulted in decreased Odora cell differentiation in vitro. Our results identify a conserved
mechanism by which microbiota regulate vertebrate olfactory transcriptional programs and
reveal a new role for REST in sensory organs.
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