Science Current Events | Science News | Brightsurf.com
 
Email a Friend Send to a friend
Printer Friendly Print Scientists discover why teeth form in a single row

Scientists discover why teeth form in a single row

February 27, 2009

Same study uncovers how each tooth signals the next to start growing

A system of opposing genetic forces determines why mammals develop a single row of teeth, while sharks sport several, according to a study published today in the journal Science. When completely understood, the genetic program described in the study may help guide efforts to re-grow missing teeth and prevent cleft palate, one of the most common birth defects.




Gene expression is the process by which information stored in genes is converted into proteins that make up the body's structures and carry its messages. As the baby's face takes shape in the womb, the development of teeth and palate are tightly controlled in space and time by gene expression. Related abnormalities result in the development of teeth outside of the normal row, missing teeth and cleft palate, and the new insights suggest ways to combat these malformations.

The current study adds an important detail to the understanding of the interplay between biochemicals that induce teeth formation, and others that restrict it, to result in the correct pattern. Specifically, researchers discovered that turning off a single gene in mice resulted in development of extra teeth, next to and inside of their first molars. While the study was in mice, past studies have shown that the involved biochemical players are active in humans as well.

"This finding was exciting because extra teeth developed from tissue that normally does not give rise to teeth," said Rulang Jiang, Ph.D., associate professor of Biomedical Genetics in the Center for Oral Biology at the University of Rochester Medical Center, and corresponding author on the Science paper. "It takes the concerted actions of hundreds of genes to build a tooth, so it was amazing to find that deleting one gene caused the activation of a complete tooth developmental program outside of the normal tooth row in those mice. Finding out how the extra teeth developed will reveal how nature makes a tooth from scratch, which will guide tooth regeneration research."

Why Extra Teeth Formed

When we lose our baby teeth, the permanent teeth grow in to replace them, but permanent teeth when lost are lost for good. U.S. adults aged 20 years and older are missing an average of four teeth due to gum disease, trauma or congenital defects. Tooth loss makes chewing difficult, causes speech problems, accelerates oral disease, and disfigures the face. Current treatments for missing teeth include dentures or dental implants, but each procedure comes with disadvantages. The idea of growing teeth to replace missing ones has captured the imaginations of scientists, with many labs investigating ways to regenerate teeth.

In the current study, Jiang and colleagues generated mice that lacked the oddskipped related-2 (Osr2) gene, which encodes one of many transcription factors that turn genes on or off. "Knocking out" (deleting) the Osr2 gene resulted in cleft palate, a birth defect where the two halves of the roof of the mouth fail to join up properly, leaving a gap. Secondly, and surprisingly, the Osr2 "knockout" mice developed teeth outside of the normal tooth row. Jiang decided to focus his research first on the effect of Osr2 on teeth patterning (vs. cleft palate) because much more was known at the time about teeth development pathways.

Although teeth usually do not become visible until after birth, their formation starts early in development. Teeth develop from the epithelium and mesenchyme, two key tissue layers within the mammalian embryo. The first sign of tooth development in mammals is the thickening of the epithelium along the jaw line to form a band of cells called the dental lamina. Because all teeth subsequently form from the dental lamina, the assumption was that some special quality of epithelial cells there made them "tooth competent." Classical experiments, however, found that the developing tooth mesenchyme was capable of inducing tooth formation from epithelial tissues that normally would not participate in tooth development. Researchers confirmed that it was indeed the mesenchyme that carried tooth initiation signals later in development, but how those signals were restricted to the area beneath the tooth row was unknown.

Past studies in other labs had shown bone morphogenic protein 4 (BMP4) to be an important factor for the initiation of teeth, and that a protein called Msx1 amplifies the BMP4 tooth-generating signal. Jiang and colleagues suggested for the first time that some unknown factor was restricting the growth of teeth into one row by opposing the Bmp4 signal.

The current study provides the first solid proof that the precise space where mammals can develop teeth (the "tooth morphogenetic field") is shaped and restricted by the effect of Osr2 on the expression of the Bmp4 gene within the mesenchymal cell layer. Jiang's team has shown not only that removing the Osr2 gene results in extra teeth outside of the normal row, but also that Osr2 is expressed in increasing concentration in the jaw mesenchyme as you move from the cheek toward the tongue in the mouse embryo, the exact opposite of the BMP4 concentration gradient. Osr2 restricts Bmp4 expression to the tooth mesenchyme under the dental lamina, and in Osr2's absence, Bmp4 gene expression expands into the jaw mesenchyme outside of the tooth row.

A second major finding of the study backs up another emerging theory which holds that careful regulation of competing pro- and anti-tooth initiation signals controls how mammalian teeth come one by one in sequence. As each tooth develops, something must prevent it from forming too close to the next or mammals would have no gaps between their teeth. When this mechanism occasionally falters, adjacent teeth come in fused together. Since evolution is not perfect, wisdom teeth (third molars) often come in too close to their predecessors, and must be pulled to make space.

Jiang and colleagues also engineered a group of mice with both the Osr2 and Msx1 genes removed. While mice without Msx1 failed to grow any teeth, mice lacking both Msx1 and Osr2 grew the first molars, but no additional teeth. Thus, without Osr2, enough BMP4 was expressed for the first molar teeth to grow, but without Msx1, the BMP4 signal was not amplified to the point where it could kick off the next tooth in the row. With these results, Jiang argues that BMP4 cooperates with other factors to create a temporary zone around each tooth where no other tooth can grow. When the tooth gets closer to maturity, Msx1 overwhelms decreasing levels of inhibitory factors to start the BMP4-driven development of the next tooth. Since the jaw is growing at the same time teeth are forming, it follows that each tooth must also receive signals that enough jaw has grown in for the next tooth to start forming atop it.

The implications of the current results may go beyond tooth development, researchers said. Thanks to the work of Jiang and others, some of the biochemical pathways involved in cleft lip/cleft palate development are now recognized, and may include BMP4, Msx1 and OSR2 as well as several others. In humans, Msx1 mutations have been linked with cleft lip/palate and with the failure to develop one or more teeth. In the next phase of the team's work, researchers will look at what other factors may be regulated by Msx1 and Osr2 to begin pinpointing the genetic network that controls teeth patterning and palate development. Their goal is to manipulate stem cells to treat malformations and to develop prevention strategies for cleft palate (e.g. the inclusion of folic acid in prenatal vitamins prevents neural tube defects in some cases). Cleft lip/palate occurs one in 700 live births.

Along with Jiang, the work was led by Zunyi Zhang and Yu Lan within the Center for Oral Biology and Department of Biomedical Genetics at the Medical Center. Yang Chai collaborated on the effort from the Center for Craniofacial Molecular Biology at University of Southern California School of Dentistry in Los Angeles. The work was sponsored by the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health.

"Beyond medical applications, our results suggest that diversity in the number of tooth rows across species may be due to evolutionary changes in the control of the BMP4/Msx1 pathway," Jiang said. "In mammals, Osr2 suppresses this pathway to restrict teeth within a single row."

University of Rochester Medical Center



Related Teeth Current Events and Teeth News Articles Teeth Current Events and Teeth News RSS Teeth Current Events and Teeth News RSS
Male sabertoothed cats were pussycats compared to macho lions
Despite their fearsome fangs, male sabertoothed cats may have been less aggressive than many of their feline cousins, says a new study of male-female size differences in extinct big cats.

The humble beginnings of a king
Tyrannosaurus rex and related large carnivorous dinosaurs together form the family Tyrannosauridae. A long forgotten fossil skull in the collections of the Natural History Museum in London has now provided crucial clues to the early stages of the lengthy evolutionary history of these fearsome predators.

AAP supports the IDF guideline on oral health for people with diabetes
New clinical guidelines released by the International Diabetes Foundation (IDF) emphasize the importance of periodontal health for people with diabetes.

American Dietetic Association Releases Updated Position Paper Promoting and Supporting Breastfeeding
The American Dietetic Association has released an updated position paper on breastfeeding that details health benefits for both infants and mothers and encourages promotion of breastfeeding whenever possible.

The largest bat in Europe inhabited northeastern Spain more than 10,000 years ago
Spanish researchers have confirmed that the largest bat in Europe, Nyctalus lasiopterus, was present in north-eastern Spain during the Late Pleistocene (between 120,000 and 10,000 years ago).

Exposure to alkaline substances can result in damaged teeth
It has long been known that acids can erode tooth enamel but a new Swedish study from the Sahlgrenska Academy at the University of Gothenburg shows that strong alkaline substances can damage teeth too - substances with high pH values can destroy parts of the organic content of the tooth, leaving the enamel more vulnerable.

Taking medicine for HIV proves hard to swallow for many people
Highly active antiretroviral therapy has increased the longevity and quality of life for people living with human immunodeficiency virus. But it requires strict adherence in taking the medicine, something that is extremely difficult for many individuals to do.

2-million-year-old evidence shows tool-making hominins inhabited grassland environments
In an article published in the open-access, peer-reviewed journal PLoS ONE on October 21, 2009, Dr Thomas Plummer of Queens College at the City University of New York, Dr Richard Potts of the Smithsonian Institution National Museum of Natural History and colleagues report the oldest archeological evidence of early human activities in a grassland environment, dating to 2 million years ago.

Penn team uses self-assembly to make molecule-sized particles with patches of charge
Physicists, chemists and engineers at the University of Pennsylvania have demonstrated a novel method for the controlled formation of patchy particles, using charged, self-assembling molecules that may one day serve as drug-delivery vehicles to combat disease and perhaps be used in small batteries that store and release charge.

Study finds mercury levels in children with autism and those developing typically are the same
In a large population-based study published online today, researchers at the UC Davis MIND Institute report that after adjusting for a number of factors, typically developing children and children with autism have similar levels of mercury in their blood streams. Mercury is a heavy metal found in other studies to adversely affect the developing nervous system.
More Teeth Current Events and Teeth News Articles
Teeth

Teeth
Starring: Josh Pais, Lenny Von Dohlen, Vivienne Benesch, John Hensley, Jess Weixler
Also With: Wolfgang Held (Cinematographer), Robert Miller (Composer)

Dawn (Sundance award winner Jess Weixler) is a pretty but prim high school virgin who unknowingly has a set of mutant teeth between her legs. When a supposedly likeminded boyfriend forces himself upon her, Dawn's vagina dentata start chomping -- which is just the beginning of "the most twisted story of female empowerment ever told" (DreadCentral.com).

Inside (Unrated)

Inside (Unrated)
Starring: Beatrice Dalle, Alysson Paradis, Nathalie Roussel, François-Régis Marchasson, Jean-Baptiste Tabourin
Directed By: Julien Maury, Alexandre Bustillo

Four months after pregnant Sara loses her husband in a horrific auto accident, she is visited on Christmas Eve by a mysterious madwoman. Alone and desperate to save her unborn child, Sara fights to stay alive as each of her potential rescuers die at the womans sadistic hands.

GNARLY TEETH SET

GNARLY TEETH SET
by Accoutrements

This Set comes with 9 different styles of teeth for every occasion. Made of plastic/soft rubber. Place this over your front teeth to give you that special look. Easy to use.

Frontier(s)

Frontier(s)
Starring: Karina Testa, Aurélien Wiik, Patrick Ligardes, Samuel Le Bihan, Estelle Lefébure
Directed By: Xavier Gens
Also With: Xavier Gens (Writer), Bertrand Ledélézir (Producer), Eric Garoyan (Producer), Frederic Ovcaric (Producer), Hubert Brault (Producer), Karim Guellaty (Producer), Laurent Tolleron (Producer)

Alone in a Paris plagued by deadly race riots the young and beautiful Yasmine is looking for a way out. In her desperation she turns to her shady ex-boyfriend. Together with his two thug friends they pull off a bold heist and head for the border. With the police close behind they hide out in a seemingly peaceful inn. But the mysterious innkeeper is hiding a secret more terrifying than anything they could ever imagine. Trapped in an endless maze of tunnels crawling with hungry subhuman cannibals they must fight to survive their bloody initiation into the innkeeper's evil family cult.System Requirements:Running Time: 108 minutes Language: French Subtitles: English / SpanishFormat: DVD MOVIE Genre: HORROR/DEMONS Rating: NR UPC: 031398232742 Manufacturer No: 23274

Crest Whitestrips Supreme Professional Strength 84 strips

Crest Whitestrips Supreme Professional Strength 84 strips
by Crest

These flexible, virtually invisible strips only need to be worn for 30 minutes twice a day. Give them a try; reveal your visibly whiter smile.

Broken (Unrated)

Broken (Unrated)
Starring: Nadja Brand, Eric Colvin (II), Atesh Salih, Abbey Stirling
Directed By: Adam Mason, Simon Boyes

Hope and her young daughter are abducted and brought to a remote forest by a mysterious and nameless man. As Hope is forced to undergo a series of humiliating, violent, and degrading trials, she fights desperately to escape and discover the fate of her missing daughter.

The Orphanage

The Orphanage
Starring: Belén Rueda, Fernando Cayo, Roger Príncep, Mabel Rivera, Montserrat Carulla
Directed By: Juan Antonio Bayona
Also With: Oscar Faura (Cinematographer), Fernando Velázquez (Composer)

Academy-Award nominated filmmaker Guillermo Del Toro (director of Pan's Labyrinth) presents The Orphanage, a chilling ghost story about a woman who discovers dark and horrific secrets hidden within her cherished childhood home and her desperate attempt to rescue her family from the nightmare into which she unwittingly led them.

Wind Up Chattering Teeth

Wind Up Chattering Teeth
by Schylling Toys

Classic wind up chattering teeth toy. Rolls forward as it chomps down! Ages 3 & up. Size: 1.62" x 1.5" x 1" **Not actual size as original**

Scarecrow Custom Fangs Adult

Scarecrow Custom Fangs Adult
by Scarecrow Inc.

Quick, easy, and totally realistic! These dental fit fangs use a specially formulated dental material for fitting; which forms a permanent mold of your tooth inside each fang cap. This patented approach means you get a tight, rigid, snap-fit and allows for use again and again. Kit contains everything needed to fit your fangs on the spot with no additional utensils needed. Includes one pair of custom fangs and a customizing kit. Not recommended for children under the age of 12, parental discretion advised.

2 - Professional 35% Tooth Whitening Kits with New FCP Anti-Cavity Gels / 20ml by Watts Power White

2 - Professional 35% Tooth Whitening Kits with New FCP Anti-Cavity Gels / 20ml by Watts Power White
by Direct 2u Wholesale LLC

Whiten your teeth in half the time at home with this professional strength formula by Watts Power White. This gel is formulated to store in the refrigerator for touch ups for up to 2 1/2 years... Obtain 4-8 Shades Whiter in 20 Days or Less, GUARANTEED. Only 30 minutes or less per application. We also include the Dentist recommended remineralizing gels used after bleaching to strengthen teeth and more importantly, to help teeth regain mineral balance in less than 3 hours. Without the remineralizing gel, teeth can take up to 5 days to rebalance. Remineralizing gels contain calcium, fluoride and phosphate. These are what your teeth are composed of. Professional quality 35% carbamide peroxide gel used worldwide by dentists. This formula is Made in the USA. Its going in your mouth, be safe...

© 2009 BrightSurf.com