An Expression Refinement Process Ensures Singular Odorant Receptor Gene Choice

Ishmail Abdus-Saboor, Mohammed J. Al Nufal, Maha Agha, Marion Ruinart De Brimont, Alexander Fleischmann, Benjamin M. Shykind

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Odorant receptor (OR) gene choice in mammals is a paradigmatic example of monogenic and monoallelic transcriptional selection, in which each olfactory sensory neuron (OSN) chooses to express one OR allele from over 1,000 encoded in the genome [1-3]. This process, critical for generation of the circuit from nose to brain [4-6], is thought to occur in two steps: a slow initial phase that randomly activates a single OR allele, followed by a rapid feedback that halts subsequent expression [7-14]. Inherent in this model is a finite failure rate wherein multiple OR alleles may be activated prior to feedback suppression [15, 16]. Confronted with more than one receptor, the neuron would need to activate a refinement mechanism to eliminate multigenic OR expression and resolve unique neuronal identity [16], critical to the generation of the circuit from nose to olfactory bulb. Here we used a genetic approach in mice to reveal a new facet of OR regulation that corrects adventitious activation of multiple OR alleles, restoring monogenic OR expression and unique neuronal identity. Using the tetM71tg model system, in which the M71 OR is expressed in >95% of mature OSNs and potently suppresses the expression of the endogenous OR repertoire [10], we provide clear evidence of a post-selection refinement (PSR) process that winnows down the number of ORs. We further demonstrate that PSR efficiency is linked to OR expression level, suggesting an underlying competitive process and shedding light on OR gene switching and the fundamental mechanism of singular OR choice.

Original languageEnglish
Pages (from-to)1083-1090
Number of pages8
JournalCurrent Biology
Volume26
Issue number8
DOIs
Publication statusPublished - 25 Apr 2016

Fingerprint

Odorant Receptors
Genes
genes
Alleles
alleles
Nose
odorant receptors
Neurons
Olfactory Receptor Neurons
Feedback
Mammals
olfactory bulb
Networks (circuits)
sensory neurons
Olfactory Bulb

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Abdus-Saboor, I., Al Nufal, M. J., Agha, M., Ruinart De Brimont, M., Fleischmann, A., & Shykind, B. M. (2016). An Expression Refinement Process Ensures Singular Odorant Receptor Gene Choice. Current Biology, 26(8), 1083-1090. https://doi.org/10.1016/j.cub.2016.02.039

An Expression Refinement Process Ensures Singular Odorant Receptor Gene Choice. / Abdus-Saboor, Ishmail; Al Nufal, Mohammed J.; Agha, Maha; Ruinart De Brimont, Marion; Fleischmann, Alexander; Shykind, Benjamin M.

In: Current Biology, Vol. 26, No. 8, 25.04.2016, p. 1083-1090.

Research output: Contribution to journalArticle

Abdus-Saboor, I, Al Nufal, MJ, Agha, M, Ruinart De Brimont, M, Fleischmann, A & Shykind, BM 2016, 'An Expression Refinement Process Ensures Singular Odorant Receptor Gene Choice', Current Biology, vol. 26, no. 8, pp. 1083-1090. https://doi.org/10.1016/j.cub.2016.02.039
Abdus-Saboor I, Al Nufal MJ, Agha M, Ruinart De Brimont M, Fleischmann A, Shykind BM. An Expression Refinement Process Ensures Singular Odorant Receptor Gene Choice. Current Biology. 2016 Apr 25;26(8):1083-1090. https://doi.org/10.1016/j.cub.2016.02.039
Abdus-Saboor, Ishmail ; Al Nufal, Mohammed J. ; Agha, Maha ; Ruinart De Brimont, Marion ; Fleischmann, Alexander ; Shykind, Benjamin M. / An Expression Refinement Process Ensures Singular Odorant Receptor Gene Choice. In: Current Biology. 2016 ; Vol. 26, No. 8. pp. 1083-1090.
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