A map can be a helpful guide, be it on a road trip or while studying sensory function in the body. When neurobiologist Sandeep Robert Datta and his team at Harvard Medical School began collecting gene expression data on olfactory function in mice, though, they didn’t expect to build an atlas for the nose. Nonetheless, as the researchers continued collecting data, they began to see a detailed picture of the organization of smell-sensing neurons emerge.
“Identifying and characterizing this map is foundational to our understanding of smell,” Datta said. He and his team published their findings in Cell.1
The anatomy of the mouse nose is complicated with scroll-like structures that made it hard for researchers to identify gene expression patterns in the tissue. Olfactory receptors (green) are spread throughout the nose.
Datta Lab
Prior to Datta and his team’s map, researchers struggled to chart the pattern of the olfactory system because the mouse nose has scroll-like structures that make it difficult for researchers to orient themselves. Additionally, there are more than 1,000 possible smell-detecting receptors in the mouse olfactory system. The decades-long hypothesis based on earlier gene expression data was that the nose was divided into a few broad zones where a subset of these 1,000 genes would be available for neurons to express, but which receptor gene in the subset they used was selected at random, leading to a patchwork of smell detection throughout the nose.2,3
With their single-cell sequencing data of mouse nose cells, Datta and his team studied the impact of COVID-19 on the loss of smell.4 When they returned to exploring general olfactory function, the researchers noticed a trend: Depending on which receptor a neuron expressed, the cell also expressed distinct subsets of genes. By labeling cells based on their expression of certain genes or sets of genes, the researchers saw an organized pattern begin to emerge. By adding spatial transcriptomic data of smell receptors, the two techniques revealed how olfactory gene expression was coordinated from the dorsal, or back, area of the nose to the ventral, or front region. The researchers saw that programs of overlapping or distinct genes influenced what smell receptor would be expressed across the nose.
“It made the confusing anatomy of the nose clear. It allowed us to understand what was up and what was down, what was dorsal and what was ventral, and that allowed us to understand this pattern of expression of the receptors as well,” Datta said.
Pairing single-cell sequencing with spatial transcriptomics, Datta’s lab created a map of the mouse olfactory system, highlighting how the neurons are expressed in an ordered pattern. A gradient of colored dots, from pink to blue, green, and yellow, extend from the outer edge of the tissue to the inner portion of the picture. Each dot represents a receptor and its associated gene. At the bottom, an inset magnifies one region of the image calling out the corresponding gene to several points.
Datta Lab
“That’s pretty amazing,” Datta continued. “No one could imagine a mechanism that would allow the nose or any other neural tissue to organize 1,000 things precisely, and that's exactly what we have observed in the nose, that somehow neural development has sufficient precision to build this incredibly detailed map.”
Additionally, the researchers showed that the map of smell receptors in the nose matched the organization of neurons in the olfactory bulb of the brain. “The idea that you could take information that was organized in a sheet in the nose and transform that meaningfully into three dimensions in the brain in a way that was so well matched was really shocking to us, but it turns out, that's the way it works,” Datta said. This also demonstrated that smell works similarly to other senses, such as vision and hearing, where maps of the sensory organ corresponded to regions in the brain.5,6
Datta said that the olfactory map could help guide the development of future therapies to help people regain their sense of smell. Currently, his team is exploring whether the organization they identified corresponds to odor chemistry, like detecting molecules related to types of food, to help the animals detect specific scents.
Reflecting on the overall experience of creating the smell map, Datta said, “It's incredibly gratifying and really rather amazing.” He continued, “The fact that it has such a beautiful and precise organization is really a delight. It tells you that nature's always going to surprise you, and often, when it surprises you, it surprises you in a really beautiful way.”
- Brann DH, et al. A spatial code governs olfactory receptor choice and aligns sensory maps in the nose and brain. Cell. 2026.
- Ressler KJ, et al. A zonal organization of odorant receptor gene expression in the olfactory epithelium. Cell. 1993;73(3):597-609.
- Vassar R, et al. Spatial segregation of odorant receptor expression in the mammalian olfactory epithelium. Cell. 1993;74(2):309-318.
- Finlay JB, et al. Persistent post–COVID-19 smell loss is associated with immune cell infiltration and altered gene expression in olfactory epithelium. Sci Transl Med. 2022;14(676):eaad0484.
- Brewer AA, Barton B. Maps of the auditory cortex. Ann Rev Neurosci. 2016;39:385-407.
- Nauhaus I, Nielsen KJ. Building maps from maps in primary visual cortex. Curr Opin Neurobiol. 2014;24:1-6.
