Always follow your nose – On the trail of the anatomical logic of smell
The sense of smell is essential for almost all animals. It helps find food, detect dangers, and distinguish between friends and enemies. As the saying goes: You really get up my nose.
Research carried out at Helmholtz Munich has shown that different odors are detected in different areas of the nose and discovered why this might be the case, unlocking the mysteries of the sense of smell.
The sense of smell is one of the oldest of our five senses. It detects changes in the molecules and chemicals floating in the air to alert us for danger or opportunity. We possess olfactory receptors (ORs) in the olfactory mucosa (OM) in our nose that bind the odor compound and send a signal through the olfactory system to the parts of our brains that identify the type of smell. The olfactory path from odorant detection to perception is very fast, which allows us to react quickly to changes in our environment.
Researchers provide the first roadmap of the mouse olfactory mucosa
Smelling plays a key role in everybody’s life. Nevertheless, little is known about how we can distinguish the various odorants effectively and whether the spatial localization of the receptors in the mucosa is thereby a crucial factor.
To unravel the anatomical logic of smell, a team of researchers led by Helmholtz Munich and Sidra Medicine generated a 3D high-resolution transcriptomic atlas of the mouse olfactory mucosa for the first time. “We employed Tomo-seq, a powerful RNA-sequencing method that gave us the information about the spatial expression pattern of any gene in the OM”, said Mayra Ruiz, one of the first authors of the study and a PhD student in the Scialdone group.
Combining Tomo-seq with machine learning algorithms, the researchers were able to characterize the spatial localization of ~18,000 genes on the OM, including 1386 unique OR genes. In doing so, they have identified five expression zones present in the mouse olfactory mucosa. “This led us to the question: Is the zonal distribution of ORs linked to the type of ligand they detect? Or better said: Is there an anatomical logic of smell?” explained Luis Saraiva from Sidra Medicine, one of the corresponding authors.
Resolving the mystery behind the anatomical logic of smell
In an outstanding effort, the researchers correlated more than 1200 physicochemical properties of odorants, such as their molecular weight, aromaticity, lipophilicity, and mucus solubility, to the location of ORs detecting them. And they found a significant association between the zonal distribution of the ORs to the mucus solubility of their cognate ligands.
“Our study provides evidence that the spatial zones in the OM enable organisms, potentially also humans, to effectively discriminate different odors”, said Antonio Scialdone, a corresponding author. “We were able to decipher the anatomical logic of smell. There are still many open questions in the olfaction field, and our findings together with the 3D transcriptomic atlas we built will help answer them”. As part of their work, the researchers created a browsable 3D gene expression atlas of the mouse olfactory mucosa, made publicly available (http://atlas3dnose.helmholtz-muenchen.de:3838/atlas3Dnose).
About the people
Mayra L. Ruiz Tejada Segura and Antonio Scialdone are part of the Institute for Epigenetics and Stem Cells, Institute of Functional Epigenetics, and Institute of Computational Biology at Helmholtz Munich. Luis R. Saraiva, from Sidra Medicine, led the study from the Qatar side.
Ruiz et al., A 3D transcriptomics atlas of the mouse nose sheds light on the anatomical logic of smell. (2022). Cell Rep. DOI: 10.1016/j.celrep.2022.110547.