PUBLICATION

Coordination of olfactory receptor choice with guidance receptor expression and function in olfactory sensory neurons

Authors
Dang, P., Fisher, S.A., Stefanik, D., Kim, J., Raper, J.A.
ID
ZDB-PUB-180201-7
Date
2018
Source
PLoS Genetics   14: e1007164 (Journal)
Registered Authors
Raper, Jonathan
Keywords
none
Datasets
GEO:GSE103692
MeSH Terms
  • Olfactory Receptor Neurons/metabolism
  • Olfactory Receptor Neurons/physiology*
  • Neurogenesis/genetics*
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Receptors, Odorant/genetics*
  • Receptors, Odorant/metabolism
  • Receptors, Odorant/physiology*
  • Cell Differentiation/genetics
  • Animals, Genetically Modified
  • Genes, Developmental*
  • Animals
  • Olfactory Bulb/metabolism
  • Olfactory Marker Protein/metabolism
  • Olfactory Mucosa/metabolism
  • Transcriptome
  • Nerve Net/embryology
  • Nerve Net/physiology
  • Axons/physiology*
  • Embryo, Nonmammalian
  • Gene Expression Regulation, Developmental
  • Sensory Receptor Cells/metabolism
  • Sensory Receptor Cells/physiology
(all 23)
PubMed
29385124 Full text @ PLoS Genet.
Abstract
Olfactory sensory neurons choose to express a single odorant receptor (OR) from a large gene repertoire and extend axons to reproducible, OR-specific locations within the olfactory bulb. This developmental process produces a topographically organized map of odorant experience in the brain. The axon guidance mechanisms that generate this pattern of connectivity, as well as those that coordinate OR choice and axonal guidance receptor expression, are incompletely understood. We applied the powerful approach of single-cell RNA-seq on newly born olfactory sensory neurons (OSNs) in young zebrafish larvae to address these issues. Expression profiles were generated for 56 individual Olfactory Marker Protein (OMP) positive sensory neurons by single-cell (SC) RNA-seq. We show that just as in mouse OSNs, mature zebrafish OSNs typically express a single predominant OR transcript. Our previous work suggests that OSN targeting is related to the OR clade from which a sensory neuron chooses to express its odorant receptor. We categorized each of the mature cells based on the clade of their predominantly expressed OR. Transcripts expressed at higher levels in each of three clade-related categories were identified using Penalized Linear Discriminant Analysis (PLDA). A genome-wide approach was used to identify membrane-associated proteins that are most likely to have guidance-related activity. We found that OSNs that choose to express an OR from a particular clade also express specific subsets of potential axon guidance genes and transcription factors. We validated our identification of candidate axon guidance genes for one clade of OSNs using bulk RNA-seq from a subset of transgene-labeled neurons that project to a single protoglomerulus. The differential expression patterns of selected candidate guidance genes were confirmed using fluorescent in situ hybridization. Most importantly, we observed axonal mistargeting in knockouts of three candidate axonal guidance genes identified in this analysis: nrp1a, nrp1b, and robo2. In each case, targeting errors were detected in the subset of axons that normally express these transcripts at high levels, and not in the axons that express them at low levels. Our findings demonstrate that specific, functional, axonal guidance related genes are expressed in subsets of OSNs that that can be categorized by their patterns of OR expression.
Genes / Markers
Figures
Figure Gallery (3 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
fh278
    Point Mutation
    p200TgTransgenic Insertion
      p201TgTransgenic Insertion
        p202TgTransgenic Insertion
          rw035TgTransgenic Insertion
            sa1485
              Point Mutation
              ti272z
                Point Mutation
                zf1062TgTransgenic Insertion
                  zf1063TgTransgenic Insertion
                    1 - 9 of 9
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                    Human Disease / Model
                    No data available
                    Sequence Targeting Reagents
                    No data available
                    Fish
                    Antibodies
                    No data available
                    Orthology
                    No data available
                    Engineered Foreign Genes
                    Marker Marker Type Name
                    CitrineEFGCitrine
                    EGFPEFGEGFP
                    GAL4EFGGAL4
                    mRFPEFGmRFP
                    1 - 4 of 4
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                    Mapping
                    No data available