A microscope cross-section image of a mouse nose, showing the anatomical structure of the nasal epithelium. Credit: Datta Lab
Olfactory receptors in the mouse nose have been mapped out in unprecedented detail — overturning researchers’ understanding of how noses build a sense of smell.
The research, published today1 in Cell, shows how around 1,100 olfactory receptors expressed on sensory neurons are organized in tightly regulated spatial locations in the epithelial tissue that lines the nasal cavity. These nasal receptor maps match smell maps in the olfactory bulb of the brain.
“For 30 years, we’ve taught students that the mouse olfactory epithelium is divided into a handful of broad zones, within which receptor choice is essentially random,” says Johan Lundström, a psychologist and experimental neuroscientist at the Karolinska Institute in Stockholm.
“This is a landmark paper that overturns one of the foundational textbook models of olfactory organization,” he adds.
Smell stripes
In the study, researchers examined about five million neurons from hundreds of individual mice. They first used single-cell sequencing to identify which smell receptors were expressed by neurons in the nose, and then used spatial transcriptomics to map out where key genes are being expressed. This allowed them to pinpoint where the receptors are and show that they are always arranged in horizontal stripes running from the top of the nose to the bottom.
“Each receptor adopts a particular position in the nose. Since there are a thousand positions in the nose, each receptor is expressed basically in a stripe that overlaps with other receptor stripes, in a thousand overlapping stripes,” says study co-author Sandeep Robert Datta, a neurobiologist at Harvard Medical School in Boston, Massachusetts.
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Datta and his colleagues proposed that this spatial mapping is organized during development and is controlled by sets of genes. The authors found that a molecule called retinoic acid had a key role in this process. They found a gradient in the amount of retinoic acid present at different points in the nose. By tweaking how much this molecule is expressed, they showed that it helped to control gene activity, guiding each neuron to express the correct type of smell receptor for its location.
“There’s been a ton of back and forth in the field about how this is all mapped out, and this nails it. I think it really changes the way people think about the olfactory system and just solves a huge problem in the field about how the mapping happens,” says Joel Mainland, an olfactory neuroscientist at the Monell Chemical Senses Center in Philadelphia, Pennsylvania.
