Krivanek Lab

In rodents and some other species, a unique adaptation has been evolved: ever-growing teeth. Such teeth, in addition to giving these species a special evolutionary advantage, it also allows us to study important aspects of developmental biology, such as stem cell niche behaviour, regeneration or tissue micropatterning during gradual differentiation in detail. Thus, continuously growing teeth play important role in several our projects.

Dentin has a very limited reparative and regenerative capacity. When it is damaged (e.g. by tooth decay) resulting in inflammation can cause irreversible changes to its structure often followed by devitalization or its loss. Obtaining dentin-producing cells that have potential to improve the healing of such damaged teeth is one of the main goals of current regenerative dentistry. Inspired by the knowledge of tooth development acquired by single-cell analyses of continuously growing teeth, we develop novel approaches to obtain functional odontoblasts from patient-derived induced pluripotent stem cells.

Teeth are formed as a result of reciprocal interactions between dental epithelium and the underlying ectomesenchyme. These precisely controlled processes result in the formation of an interesting micropatterning inside both dentin and enamel.

We have recently shown that different types of interacting dental epithelium influence odontoblasts to generate dentins of different quality. These differences range from the morphology of the odontoblast processes to the mineralization quality of the crown and root dentins. Our results also suggest that this process is controlled by Wnt signaling (Lavicky et al., JBMR, 2022).

Unlike dentin, adult enamel exhibits a unique prismatic micropatterning resulting from accurately synchronized movements of ameloblasts in dental epithelium. It has been known for decades that enamel rods alternate positions and overlap with each other, forming peculiar decussation patterns. However, there is still no explanation of how these patterns are formed, and how is this process regulated. Using advanced imaging techniques (including lightsheet, confocal and scanning electron microscopy), genetically modified organisms and in vivo imaging, we are uncovering this decades old mystery.

Mechanotransduction plays an important role in numerous developmental processes, including cell proliferation or differentiation. The main aim of this project is to determine the role of mechanosensing in regulation of tooth growth and dental tissue repair. As a key model we use mouse incisors and molars, however we also work with other vertebrates which help us to uncover if mechanosensing is a general mechanism acquired by all vertebrates regardless of the morphology of tooth-bone area during odontogenesis. This project helps to understand cellular processes involved in reparative and regenerative odontogenesis but also to tackle more general questions that extend beyond the dental field, and will provide new insight into the regulation of developmental and healing processes of hard tissues.

We investigate the cellular composition of stem cell niche, its intricate dynamics during homeostasis and response to injury, fate decisions, and its establishment during embryonic development.