PUBLICATION

Commensal bacteria regulate gene expression and differentiation in vertebrate olfactory systems through transcription factor REST

Authors
Casadei, E., Tacchi, L., Lickwar, C.R., Espenschied, S.T., Davison, J.M., Muñoz, P., Rawls, J.F., Salinas, I.
ID
ZDB-PUB-190814-4
Date
2019
Source
Chemical senses   44(8): 615-630 (Journal)
Registered Authors
Davison, James M., Espenschied, Scott "Ted", Lickwar, Colin, Rawls, John F.
Keywords
germ-free, mice, olfactory receptors, olfactory sensory neurons, transcriptomics, zebrafish
MeSH Terms
  • Animals
  • Cell Line
  • Conserved Sequence
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Germ-Free Life
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microbiota/physiology*
  • Nerve Tissue Proteins/genetics*
  • Nerve Tissue Proteins/metabolism
  • Olfactory Mucosa/cytology
  • Olfactory Mucosa/metabolism*
  • Olfactory Mucosa/microbiology
  • Olfactory Receptor Neurons/cytology
  • Olfactory Receptor Neurons/metabolism*
  • Olfactory Receptor Neurons/microbiology
  • Promoter Regions, Genetic
  • Protein Binding
  • Protein Isoforms/genetics
  • Protein Isoforms/metabolism
  • Rats
  • Repressor Proteins/genetics*
  • Repressor Proteins/metabolism
  • Smell/genetics*
  • Symbiosis/physiology
  • Zebrafish
PubMed
31403159 Full text @ Chem. Senses
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 was 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. REST (RE1 silencing transcription factor, also called NRSF) is a zinc finger transcription factor 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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping