Press Release: A Czech Scientist is Document Tooth Development. The discovery can help in the fight against cancer (6.5.2016)

Mammal teeth start developing as early as during the embryonic stage and it is only a question of time when the first tooth cuts its way through the gums in a newborn. The manner of how the position of future teeth in the jawbone is determined was described and recorded in real time by researchers from the University of California in San Francisco. The main credit for this discovery goes to a young Czech scientist, Mgr. Jan Procházka, Ph.D., who returned to the Czech Republic after several years of postdoctoral studies in the US. He completed his research in the Czech Center for Phenogenomics, a part of the BIOCEV research center.

The basic scientific knowledge that resulted from this research is that mammal epithelium cells, which previously were considered to be a very tight and rigid structure, are capable of targeted movement. Moreover, teeth are an important model for studying the development of other organs because universal development programmes widely apply to them. Therefore, we can assume that the described epithelium migration is most likely a more general mechanism of organ formation throughout the entire animal kingdom. This would also explain why the positions of teeth and other organs differ so much among species even though their early cellular precursors are the same.

It is also important for clinical practice that the migration observed in molar precursors is, in many aspects, similar to the behaviour of invasive cancer cells. A deeper understanding of the organ precursor migration mechanism during the embryonic stage can also be of vital importance to the research into cancer formation and invasive proliferation.

Migrating cells

Morphogens, signal molecules that diffuse in tissue, play an important role for organs to develop in the correct place during the embryonic stage. As morphogens diffuse, concentration gradients form in the embryo — the concentration of these substances varies at different distances from the source. Their concentration levels determine which types of specialised cells and which organs form in a given location.

The generally accepted theory behind tooth development holds that the signal for their development is an interaction between epithelial cells in the cavity, producing the Sonic Hedgehog (SHH) protein, a well-known morphogen, and the cells of mesenchyme, which sends a signal to the upper and lower jaws. The dental lamina and tooth buds are then formed as the foundations of future teeth. But what happens before this inside the actual epithelium? Do some other cells participate in the formation of tooth foundation? And how do these cells get to the right place?

Research has shown that precursor epithelium cells predetermined for molar formation do not develop in the location of a future tooth from the beginning, as scientists previously believed, but instead migrate to their final position during development. Using a microscope with a camera, Jan Procházka and his co-workers recorded how cells that turn into molars later change their position over two days during embryonic development in mice. Such cells first form a rosette structure in the back of the cavity near the jaw joint; the rosette than travels to the location where the tooth later grows. Further observation has shown that the during the process, cells producing the SHH morphogen are found in the final location of precursor cells, showing future molar cells the path to their final home. When researchers blocked SHH protein production in mice, both targeted cell migration and tooth development were disturbed.

More information can be found in the following publication:
Prochazka J, Prochazkova M, Du W, Spoutil F, Tureckova J, Hoch R, Shimogori T, Sedlacek R, Rubenstein JL, Wittmann T, Klein OD. Migration of Founder Epithelial Cells Drives Proper Molar Tooth Positioning and Morphogenesis. Dev Cell. 2015 Dec 21;35(6):713-24. doi: 10.1016/j.devcel.2015.11.025.

The BIOCEV Center is a common project implemented by six institutes of the Czech Academy of Sciences and Charles University in Prague under the Operational Programme Research and Development for Innovation. The beneficiary and the main guarantor is the Institute of Molecular Genetics of the Czech Academy of Sciences. By 2020, 450 researchers, of which 200 will be PhD students, are expected to work in the Biotechnology and Biomedicine Center in Vestec. The Center’s main objective is to learn details about organisms at the molecular level that will be used in applied research and in the development of new therapeutic procedures.

The Czech Center for Phenogenomics (CCP) is one of the six BIOCEV research institutes and the largest institute of its kind in Central Europe. CCP will also work as a transgenic laboratory producing specialised, genetically modified mice that are used as tools for the research of gene functions by both the Czech and international scientific communities. Together with foreign co-workers, Radislav Sedláček, the Head of the CCP, and his team are working in the international programme entitled the Encyclopaedia of Mammalian Gene Functions, which is focused on the primary description of functions of all genes over the next ten years. The results of their research may positively affect the treatment of serious illnesses.

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