Genetic Ablation of Type III Adenylyl Cyclase Exerts Region-Specific Effects on Cilia Architecture in the Mouse Nose.

Rosemary C Challis,Wenbin Yin,Minghong Ma,Huikai Tian,Kazushige Touhara

doi:10.1371/journal.pone.0150638

Rosemary C Challis, Wenbin Yin + Show 3 more

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https://doi.org/10.1371/journal.pone.0150638

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Abstract

We recently reported that olfactory sensory neurons in the dorsal zone of the mouse olfactory epithelium exhibit drastic location-dependent differences in cilia length. Furthermore, genetic ablation of type III adenylyl cyclase (ACIII), a key olfactory signaling protein and ubiquitous marker for primary cilia, disrupts the cilia length pattern and results in considerably shorter cilia, independent of odor-induced activity. Given the significant impact of ACIII on cilia length in the dorsal zone, we sought to further investigate the relationship between cilia length and ACIII level in various regions throughout the mouse olfactory epithelium. We employed whole-mount immunohistochemical staining to examine olfactory cilia morphology in phosphodiesterase (PDE) 1C-/-;PDE4A-/- (simplified as PDEs-/- hereafter) and ACIII-/- mice in which ACIII levels are reduced and ablated, respectively. As expected, PDEs-/- animals exhibit dramatically shorter cilia in the dorsal zone (i.e., where the cilia pattern is found), similar to our previous observation in ACIII-/- mice. Remarkably, in a region not included in our previous study, ACIII-/- animals (but not PDEs-/- mice) have dramatically elongated, comet-shaped cilia, as opposed to characteristic star-shaped olfactory cilia. Here, we reveal that genetic ablation of ACIII has drastic, location-dependent effects on cilia architecture in the mouse nose. These results add a new dimension to our current understanding of olfactory cilia structure and regional organization of the olfactory epithelium. Together, these findings have significant implications for both cilia and sensory biology.

Highlights

Cilia are remarkably diverse in their numbers, lengths, and morphologies and are well-suited for mediating various cellular functions, such as fluid transport, cell motility, and detection of sensory stimuli [1, 2]
These data support the hypothesis that ACIII level is positively correlated with olfactory cilia length and provide additional evidence that ACIII may be involved in regulating cilia growth and the establishment of the cilia pattern in the dorsal zone
We provide further evidence that ACIII level is positively correlated with olfactory cilia length in the dorsal zone of the main olfactory epithelium

Summary

Introduction

Cilia are remarkably diverse in their numbers, lengths, and morphologies and are well-suited for mediating various cellular functions, such as fluid transport, cell motility, and detection of sensory stimuli [1, 2]. ACIII and Olfactory Cilia Architecture shape) and function are regulated in different cell types is critical for the future therapeutic treatment of these disorders. The mammalian olfactory system is a unique model for studying cilia structure and function, given that olfactory sensory neurons (OSNs) in the mouse nose possess cilia with different lengths and sensitivities, depending on the cell location in the olfactory epithelium [6]. Each OSN can possess up to 30 immotile cilia, which extend in a star-like arrangement from the dendritic knob and house the key proteins involved in olfactory signal transduction [7, 8]. Termination and adaptation of the olfactory response is critical for proper olfactory signaling and is mediated in part by phosphodiesterases (PDEs), which hydrolyze cAMP to AMP [11]

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