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Developmental biology - Development of Smell

How Smelling Works

A dog's nose knows scent better than a human's - why is that?...


Dogs are known for their extraordinary sense of smell. They can find scents as subtle as that of a bed bug. But, they are famous for sniffing out drugs, bombs, missing hikers and even cancers. This is because they have a flat sheet of tissue lining their nasal cavity called the olfactory epithelium. In dogs, however, their olfactory epithelium is more complex than any other animal's, particularly humans.

Dogs' olfactory epithelial cells form a maze, folding and curling over a number of bony protrusions called turbinates that exist only in a dog's nasal cavity. Special neurons located inside their olfactory epithelium bind to odor molecules in order to transmit these molecular signals to the brain where they are interpreted as unique scents. Due to their numerous turbinates, the area covered by their epithelial layer is significantly magnified. So dogs have hundreds of millions more neurons than people.

Olfactory structure for mouse

In experiments, the olfactory structure of the mouse acts as a model for the dogs' superior ability to smell. Surprisingly, an observed fact that had never been proven scientifically.

Now, researchers at Washington University School of Medicine in St. Louis have uncovered new details in how the olfactory epithelium develops. This new knowledge could help scientists prove that turbinates and the resulting larger surface area of the olfactory epithelium that wraps around them, is the one definitive reason dogs smell so well.
"We think the surface area of the [epithelial]sheet matters in how well animals smell and in the types of smells they can detect. One reason we think this stems from differences in the complexity of these turbinates. Animals that we think of as having a great sense of smell have really complex turbinate systems."

David M. Ornitz MD PhD, the Alumni Endowed Professor of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri, USA.

The study, published Aug. 9 in the journal Developmental Cell, could help answer the longstanding question: Why do animals' senses of smell so enormously vary? The way they came to diverge over evolutionary history remains a mystery. Understanding these signals could help scientists tease out how humans wound up with a such comparatively stunted one.

First author Lu M. Yang, a graduate student in Ornitz's lab, found that a newly discovered stem cell - called FEP - controls the size of the surface area of the olfactory epithelium. FEP stem cells send a specific signaling molecule to the underlying turbinates, stimulating them to grow.
Evidence suggests this signal crosstalk between FEP epithelial cells and the bony turbinates, ends up regulating the scale of the olfactory system, sometimes resulting in an olfactory epithelium with a larger surface area, like that in dogs.

When stem cells can't signal properly, turbinates stop growing and olfactory epithelial surface area stops development. To study this in the lab, mice with olfactory stunting were compared with typical mice to learn more about how FEP signals govern an animal's olfactory system.

"Before our study, we didn't know how the epithelium expands from a tiny patch of cells into a large sheet in conjunction with complex turbinates," Lu M. Yang explains. "We can use this information to help understand why dogs have such a good sense of smell. They have extremely complex turbinate structures, and now we know some details about how those structures develop."

Highlights
Fgf20-positive epithelial-spanning progenitor (FEP) cells form olfactory epithelium
FEP cells regulate turbinate growth via FGF20
Wnt/?Cat signaling maintains FEP cells in an undifferentiated state
Wnt/?Cat signaling regulates the expression of FGF20

Summary
The olfactory epithelium (OE) is a neurosensory organ required for the sense of smell. Turbinates, bony projections from the nasal cavity wall, increase the surface area within the nasal cavity lined by the OE. Here, we use engineered fibroblast growth factor 20 (Fgf20) knockin alleles to identify a population of OE progenitor cells that expand horizontally during development to populate all lineages of the mature OE. We show that these Fgf20-positive epithelium-spanning progenitor (FEP) cells are responsive to Wnt/-Catenin signaling. Wnt signaling suppresses FEP cell differentiation into OE basal progenitors and their progeny and positively regulates Fgf20 expression. We further show that FGF20 signals to the underlying mesenchyme to regulate the growth of turbinates. These studies thus identify a population of OE progenitor cells that function to scale OE surface area with the underlying turbinates.

Authors: Lu M. Yang, Sung-Ho Huh, David M. Ornitz.


Acknowledgements
The authors would like to thank Dr. Alwyn H.A Derijck for valuable feedback.

This work was funded by the March of Dimes Foundation; the National Institutes of Health (NIH), grant numbers HL111190 and DC012825; the Department of Developmental Biology at Washington University; the HOPE Center Alafi Neuroimaging Laboratory, grant number NCRR 1S10RR027552; and the Washington University Center for Cellular Imaging of the Children's Discovery Institute, grant numbers CDI-CORE-2015-505 and NS086741.

Washington University School of Medicine's 1,300 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.


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Aug 17, 2018   Fetal Timeline   Maternal Timeline   News   News Archive




The olfactory epithelium [GREEN] of a mouse - a sheet of tissue that develops in the nasal cavity. Researchers found new details on how it develops and why some animals have a greater sense of
smell than others. Image Credit: Washington University School of Medicine, USA.


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