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Expression of cGMP signaling elements in the Grueneberg ganglion

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The Grueneberg ganglion (GG) is a cluster of neurons localized to the vestibule of the anterior nasal cavity. Based on axonal projections to the olfactory bulb of the brain, as well as expression of olfactory receptors and the olfactory marker protein, it is considered a chemosensory subsystem. Recently, it was observed that in mice, GG neurons respond to cool ambient temperatures. In mammals, coolness-induced responses in highly specialized neuronal cells are supposed to rely on the ion channel TRPM8, whereas in thermosensory neurons of the nematode worm Caenorhabditis elegans, detection of environmental temperature is mainly mediated by cyclic guanosine monophosphate (cGMP) pathways, in which cGMP is generated by transmembrane guanylyl cyclases. To unravel the molecular mechanisms underlying coolness-induced responses in GG neurons, potential expression of TRPM8 in the murine GG was investigated; however, no evidence was found that this ion channel is present in the GG. By contrast, a substantial number of GG neurons was observed to express the transmembrane guanylyl cyclase subtype GC-G. In the nose, GC-G expression appears to be confined to the GG since it was not detectable in other nasal compartments. In the GG, coolness-stimulated responses are only observed in neurons characterized by the expression of the olfactory receptor V2r83. Interestingly, expression of GC-G in the GG was found in this V2r83-positive subpopulation but not in other GG neurons. In addition to GC-G, V2r83-positive GG cells also co-express the phosphodiesterase PDE2A. Thus, in summary, coolness-sensitive V2r83-expressing GG neurons are endowed with a cGMP cascade which might underlie thermosensitivity of these cells, similar to the cGMP pathway mediating thermosensation in neurons of C. elegans.

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Carbonic anhydrase subtype II


Cyclic guanosin monophosphate




Grueneberg ganglion


Transmembrane guanylyl cyclase


Main olfactory epithelium


Olfactory bulb


Olfactory marker protein


Olfactory sensory neurons




Reverse transcriptase polymerase chain reaction


Trace amine-associated receptor


Transient receptor potential


Vomeronasal organ


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We would like to thank Bela Zimmer and Roman Weber for excellent technical assistance. We are indebted to Karin Schwarzenbacher for helpful discussion and critical comments on the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft.

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Correspondence to Joerg Fleischer.

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J. Fleischer and K. Mamasuew contributed equally to this work.

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Supplemental Fig. 1 Position of OMP-positive GG neurons in the anterior nasal region. A Schematic drawing representing a sagittal section through a mouse head (adapted from Fleischer et al. 2007). The localization of the GG, the VNO, the MOE, and the OB is given. The axonal projections of GG neurons to the OB are indicated. The broken line denotes the coronal section plane shown in B-C. B Coronal section through the anterior nasal region of a neonatal mouse hybridized with an OMP-specific antisense riboprobe. The OMP-expressing GG neurons are situated between the nasal roof, the nasal cavity, and the septum. C Higher magnification of the boxed area in B. Scale bars: B = 200 μm; C = 50 μm (DOC 21794 kb)

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Fleischer, J., Mamasuew, K. & Breer, H. Expression of cGMP signaling elements in the Grueneberg ganglion. Histochem Cell Biol 131, 75–88 (2009).

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