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Pax9: The Gene Behind Missing Teeth

Discover how Pax9 affects tooth growth and development in zebrafish and humans.

Sandhya Paudel, Sarah McLeod, Stefani Gjorcheska, Lindsey Barske

― 7 min read


Pax9 and Teeth: A Genetic Pax9 and Teeth: A Genetic Tale and zebrafish anatomy. Exploring the impact of Pax9 on teeth
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Once upon a time in the world of genetics, there was a transcription factor named Pax9. This little guy plays a big role in how teeth and other parts of our mouths develop. But, as it turns out, Pax9 could also be a bit of a troublemaker when it comes to tooth loss, especially in Zebrafish and humans.

This article will take you on a journey through the fascinating world of Pax9, teeth, and some seriously peculiar zebrafish. Don’t worry, we’ll keep it simple and even throw in some fun facts along the way!

What is Oligodontia?

Oligodontia is a fancy term for when someone is missing six or more permanent teeth. Imagine trying to chomp down on a delicious steak with only half your teeth! It’s a real challenge. This condition can be linked to various genetic mutations, including those affecting the Pax9 gene.

When certain mutations occur, like those that cause the Pax9 protein to not work properly, people sometimes end up with smiling gaps where teeth should be.

The Role of Pax9

So, what does Pax9 actually do? This transcription factor is involved in the process of tooth development. Think of it as the conductor of an orchestra, making sure that all the right genes play their parts when it comes to forming teeth.

Pax9 helps form the tooth buds, which are the earliest stages of teeth. With over sixty different variants leading to problems with Pax9, it’s not surprising that people with these mutations can miss a lot of teeth.

Now, let’s meet our friend the zebrafish, a fish that has also been found to have some interesting connections to Pax9 and tooth development.

Zebrafish: The Fish that Lost Its Teeth

Zebrafish, the little fish often found swimming in labs, have a fascinating history. They belong to a group of fish that lost their teeth millions of years ago. Yes, you read that right! While most fish have a mouth full of teeth, the zebrafish decided to go a different route. Yet, they still have Pax9 hanging around in their genomes.

Although zebrafish don’t have teeth in their mouths like humans, they still have some tooth-like structures in the back of their mouths. These structures are called pharyngeal teeth. It’s like they couldn’t completely part with the idea of teeth.

The Mystery of Pax9 in Zebrafish

Researchers have found that even though zebrafish Pax9 is active, it doesn’t lead to any significant tooth development. This raises some questions. Why does Pax9 hang around if it hasn’t helped zebrafish grow a proper set of teeth? A possible answer could lie in the fact that Pax9 may have evolved to serve other purposes over time.

In zebrafish, Pax9 is expressed in various areas around the mouth, suggesting it still plays a role in the development of other structures, even if it doesn’t contribute directly to teeth anymore. This is where things start to get even more interesting!

The Search for Missing Bones and Barbels

Aside from not having teeth, zebrafish mutants that lack Pax9 also have some serious Skeletal issues. When scientists looked at the skeletons of these mutants, they found that many bones formed improperly or didn’t form at all. Picture a fish with a wonky jaw and missing bones; it’s both sad and a bit funny to imagine.

One notable feature that seems to go missing in Pax9 mutant zebrafish is the nasal and maxillary barbels. Barbels are those cute, whisker-like structures some fish have that help them sense their surroundings. Without Pax9, the zebrafish completely miss out on these sensory appendages.

Breaking Down the Skeletal Development

As researchers studied the bones of the Pax9 mutants, they noticed something strange. The maxilla (the bone that forms the upper jaw) and the premaxilla (the bone that forms the part of the jaw where the front teeth would be) were either missing or only partially formed. It’s like trying to build a house without windows – it’s just not going to work out!

Interestingly, even with all these skeletal issues, Pax9 mutants can still munch away on their food. It seems that their other skeletal connections and muscles work well enough for them to feed effectively, even if they look a little different while doing it.

The Role of Genes in Development

Understanding why some bones and structures don’t develop properly can be complicated. There are many genes and signals at play. In zebrafish, Pax9 interacts with other genes to help shape the development of their mouths and jaws.

When scientists explored the connections between Pax9 and these other genes, they found that Pax9 must work alongside several key players like Wnt signaling pathways that are essential for proper bone growth and development. It’s like a game of teamwork where every player has to do their part.

Not All Fish Are the Same

Now, it’s essential to note that not all fish share the same genetic story. While zebrafish may have lost the ability to grow teeth over time, other fish species still have healthy sets of teeth. This suggests that Pax9 has different functions depending on the fish in question.

In fact, when researchers looked at Pax9 in other fish species that have teeth, they found that the impacts of Pax9 mutations were quite different. This highlights the variability in how genes can influence development among different species.

Lessons from Evolution

As scientists dive deeper into understanding Pax9, they are also piecing together the story of evolution. The presence of Pax9 in various species suggests that it may have originally helped in tooth development. However, as certain species evolved, Pax9 adapted for various purposes beyond teeth.

In mammals, Pax9 plays a crucial role in forming teeth, while in zebrafish, it has shifted focus to supporting the development of other mouth-related structures. It’s a story of adaptation and change, like watching a fish evolve from a toothy predator to a more streamlined creature!

Brilliant Research Techniques

To understand the role of Pax9 better, researchers employed various techniques, including genetic manipulation and imaging methods. By creating mutant zebrafish and observing how they develop, scientists can gain critical insights into what goes wrong when Pax9 is not functioning correctly.

Using bright colors and fluorescent techniques, scientists can even visualize different cell types as they grow and develop. Think of it as putting on a pair of special glasses that allow researchers to see how genes are at work.

What’s Next for Pax9 Research?

As the world of genetics rapidly evolves, there’s still so much more to learn about Pax9 and its role in tooth development. Researchers are keen to uncover more about how this interesting transcription factor works in different species and what other functionalities it may have.

In the meantime, the journey of Pax9 will inspire many more studies, discussions, and maybe even a few chuckles about the peculiarities of zebrafish and their missing teeth and weird skeletons.

Conclusion

So, what’s the takeaway from this deep dive into Pax9 and zebrafish genetics? While Pax9 may have lost its primary job in tooth development in zebrafish, it still plays a significant role in shaping other structures around the mouth. This story highlights the dynamic nature of evolution and the fascinating world of genetics.

As we continue to explore the mysteries of genes, who knows what other surprises await in the vast ocean of biological research? One thing is for sure: the tale of Pax9 is anything but dull! And while zebrafish may not be winning any toothy smiles, at least they’ve got character.

Now, the next time you see a fish swimming around, you might just think about its genetic quirks and the incredible journey that brought it to where it is today – even if it lacks the ability to grow a full set of teeth!

Original Source

Title: Midfacial retrusion and loss of facial appendages caused by mutation of Pax9 in zebrafish

Abstract: Loss of dentition has occurred repeatedly throughout vertebrate evolution. Cyprinid fish, including zebrafish, form teeth only deep within the pharynx, not on their oral jaws. However, zebrafish still robustly express transcription factors associated with mammalian tooth development in the neural crest-derived mesenchyme surrounding the mouth. We investigated whether this expression is vestigial or whether these factors contribute to the formation of non-tooth mesenchymal structures in the oral region, using Pax9 as a test case. Zebrafish homozygous for two different pax9 mutant alleles develop the normal complement of pharyngeal teeth but fail to form the premaxilla bone, most of the maxilla, and nasal and maxillary barbels. Lack of most of the upper jaw complex does not preclude effective feeding in the laboratory environment. We observed a significant deficit of sp7:EGFP+ osteoblasts and adjacent alx4a:DsRed+ condensing mesenchyme where the maxilla forms, and no accumulation of either in the premaxillary domain. These phenotypes are not presaged by major disruptions in early facial patterning, Wnt signaling, proliferation, or cell death; however, loss of a small population of Wnt-responsive cells around the maxilla correlates with its stalled growth in mutants. We conclude that Pax9 is not unequivocally required for all vertebrate tooth development, but instead may be broadly involved in the development of a variety of organs forming through mesenchymal condensation around the mouth.

Authors: Sandhya Paudel, Sarah McLeod, Stefani Gjorcheska, Lindsey Barske

Last Update: 2024-12-13 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.12.12.628204

Source PDF: https://www.biorxiv.org/content/10.1101/2024.12.12.628204.full.pdf

Licence: https://creativecommons.org/licenses/by-nc/4.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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