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Retinoic acid receptor and CNGA2 channel signaling are part of a regulatory feedback loop controlling axonal convergence and survival of olfactory sensory neurons
Author(s) -
ztokatli Hande Ö,
Hörnberg Maria,
Berghard Anna,
Bohm Staffan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.11-192450
Subject(s) - sensory system , retinoic acid , microbiology and biotechnology , loop (graph theory) , neuroscience , biology , retinoic acid receptor , biochemistry , gene , mathematics , combinatorics
Little is known about the identities and functions of extracellular signaling molecules that work in concert with neuronal activity to regulate refinement and maintenance of the mouse olfactory sensory map. We show that expression of a dominant negative retinoic acid receptor (RAR) in olfactory sensory neurons (OSNs) increased the number of glomeruli that incorrectly contained OSN axons expressing different odorant receptors. This phenotype became apparent postnatally, coincided with increased cell death, and was preceded by increased Neuropilin‐1 and reduced Kir‐rel‐2 expressions. Kirrel‐2‐mediated cell adhesion influences odorant receptor‐specific axonal convergence and is regulated by odorant receptor signaling via the olfactory cyclic nucleotide‐gated (CNG) ion channel. Accordingly, we found that inhibited RAR function correlated with reduced CNG channel expression. Naris occlusion experiments and analysis of CNG channeldeficient mice further indicated that RAR‐regulated CNG channel levels influenced the intrinsic neuronal activity required for cell survival in the absence of odor stimulation. Finally, we showed that CNG channel activity regulated expression of the retinoic acid‐degrading enzyme Cyp26B1. Combined, these results identify a novel homeostatic feedback mechanism involving retinoic acid metabolism and CNG channel activity, which influences glomerular homogeneity and maintenance of precisely connected OSNs.—Öztokatli, H., Hörnberg, M., Berghard, A., Bohm, S. Retinoic acid receptor and CNGA2 channel signaling are part of a regulatory feedback loop controlling axonal convergence and survival of olfactory sensory neurons. FASEB J. 26, 617–627 (2012). www.fasebj.org