A couple of genes were found, the struggle of which determines the number of teeth in the mouth and the pattern of their growth. In mutant mice lacking the Osr2 gene, a second row of teeth grows, like a shark. These same genes are involved in the emergence of an innate cleft palate, so that mutant mice do not live long after birth
No matter how people boast of their superiority over all other animals, sea predators of sharks, primitive even by fish standards, have a reason to disagree. And when they use their argument, it leaves an indelible mark - if not in the soul, then on the feet of hapless surfers. We are talking, of course, about the shark's teeth, which are large and arranged in several rows. And ours are small and fit in one line (except for rare and short cases, when permanent teeth grow slightly away from milk that has not yet fallen out).
Man is not alone in his wretchedness: a single row of teeth is one of the distinguishing features of mammals among vertebrates in general. Not only sharks have a lot of dentition. Some fish have a pair of them on each jaw, in the Tuatars (tuatars) that have come down to us from the Mesozoic times, they are generally located asymmetrically, there are two rows of teeth on top, and one on the bottom.
Despite such a curious variety of dental configurations (and a considerable amount of money spinning in dentistry and spilling droplets into basic science related to this field), scientists still do not fully understand the molecular mechanisms that govern the appearance of teeth.
Who decides where and when to grow the next tooth, how does he communicate his decision to the cells that should develop into a tooth?
Why, in the end, does this "manager" not grow me a replacement for the once beautiful tooth, now eaten away by caries?
Jiang Zhulan, Zunyi Zhang, and two other American scientists at the University of Rochester and the University of Southern California believe they know who stops tooth growth. This is the Osr2 gene, which encodes a transcription factor, which in turn controls the synthesis of several tens, if not hundreds, of other proteins and factors. If not for Osr2, our teeth would grow in the most unexpected places.
Several years ago, Jiang Zhulan and his colleagues discovered that mice lacking both copies of the Osr2 gene in their chromosome set develop embryos of not one, but two rows of teeth during embryonic development. An additional row appears in at least four places - next to each of the first four molars (molars), a little closer to the tongue, another small "molar" begins to form.
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It was not possible to grow from the mouse Osr2 - / - -line (the superscript "- / -" means the absence of two copies of the indicated gene) any "shark mice" capable of destroying all grain and all cheese reserves: mutants die soon after birth due to non-union of the palate (in humans it is called the cleft palate). However, the extra dental embryos, being transplanted from the mouth of a mutant mouse into a normal one, together with the surrounding tissues, develop into quite hard, mineralized teeth - not only reference teeth, but at least similar to molars.
In their current work, the researchers tracked changes in the expression of several important genes in the dental plate (the layer above / below the jaw from which teeth develop) during the intrauterine development of normal and Osr2 - / - - mutant mice. In addition to Osr2, the Msx1 gene, another transcription factor that provokes the synthesis of the Bmp4 protein, one of the members of the family of "bone-forming" proteins, involved, according to previous studies, in initiating tooth formation, was also knocked out.
Biologists monitored changes in gene expression in a standard way - removing embryos from the mother's womb at a given time, cutting their skulls into thin layers and measuring the content of specified proteins and their "molecular schemes" - messenger RNAs from cell to cell. The research results are published in the latest issue of Science.
It is known that the most interesting happens not even in the epithelium, from which the tooth itself then grows, but in the mesenchyme - a thin layer of connective tissue located between the epithelium and the growing jaw of the embryo. As the authors of the work showed, the concentration of Osr2 in normal mice increases sharply from the dental plate towards the tongue. Conversely, the concentration of Bmp4 drops just as sharply, as if Osr2 somehow inhibits protein synthesis.
The analysis of the development of Osr2 - / - Msx1 - / - mutants became decisive for the model of tooth development.
In mice lacking both copies of both genes, firstly, an extra tooth did not grow next to the first molar, and secondly, not a single tooth grew at all besides these first molars!
At the same time, the Bmp4 protein was synthesized near the developing tooth, but in some completely unimpressive amounts.
The combination of these observations allowed the authors of the work to formulate their model of tooth development. According to Jiang, the sequence of the appearance of teeth and their distribution in the oral cavity is determined in the dialectical struggle between two transcription factors - Osr2 and Msx1. In this confrontation, Osr2 plays the role of a growth restrictor - it is he who prevents the growth of the second, third and subsequent rows of teeth, while Msx1, on the contrary, provokes the synthesis of Bmp4 and the growth of the tooth itself.
By the way, Osr2 not only prevents an additional row of teeth from growing in the mouth of mammals. The same factor forces us to make "indents" in the successive development of teeth so that they do not overlap each other; perhaps this function is its main purpose. But Osr2 does not perform it perfectly, as almost everyone who has had wisdom teeth can testify. According to Jiang, it is the "under-tuning" of the Osr2 / Msx1 system that is the reason for the insufficient indentation in this case.
So far, scientists do not see prospects for the direct application of their findings in clinical dentistry: in the near future, no one will be able to grow your lost tooth with a Bmp4 injection in the right place.
Still, there is a huge gap between a couple of genes and the development of an entire organ. Moreover, in addition to these autonomous signals, there must be some others tied to absolute age, as the story with milk teeth convincingly testifies. At the same time, Jiang and his colleagues hope that their work will help detect congenital genetic abnormalities (like the cleft palate) as early as possible, long before the baby is born. And, perhaps, even interfere in their development in some way.