7. PROJECT SUMMARY
The long-term goal of the proposed research is gain fundamental insights into the process of tooth generation
and loss using the innovative leopard gecko model. The gecko is the first biomedical research model where there
is direct access to the replacing dentition in an adult animal. Our first theme is tooth eruption. There are very few
animals in which we can study tooth eruption which is key for creating a functioning dentition. There is a poor
understanding of what drives teeth to move upwards to the oral cavity. We propose pioneering experiments
based in part on dental techniques and innovative developmental biology methods. Our experiments will test
whether teeth gain traction from attaching to dental epithelium, whether softening of the matrix above the teeth
helps to move teeth upwards. This work is fundamental to our understanding of human defects in tooth eruption,
particularly teeth that become buried in the jaw and are difficult to treat. The second theme is tooth resorption.
The gecko repeatedly loses teeth but not randomly. Instead there is timed tooth shedding that involves
odontoclasts, a cell type that is rarely studied. The unwanted activity of odontoclasts in humans causes roots to
resorb ultimately leading to premature tooth loss. The rationale for choosing the leopard gecko is as follows: 1)
the gecko discoveries are likely to be applicable to human tooth replacement due to shared evolutionary history,
2) adult geckos have large numbers of teeth that are replaced throughout life, 3) gecko teeth are only attached
to bone on the cheek side, leaving the other side accessible to experimental manipulation, 4) the tooth
replacement cycle is much shorter than other adult reptiles so a change is visible sooner, 5) gecko teeth are
regularly invaded by odontoclasts providing us with an opportunity to study odontoclast behaviour during a
normal, physiological process 6) the Richman lab initiated studies on gecko tooth replacement. We have proven
that after tooth removal that the teeth will regrow. The gecko offers unique access to the developing adult
dentition compared to mouse, fish and shark models. The ability to continually monitor the effects of dental
surgery on tooth regeneration or to odontoclast recruitment in living animals is not possible in other models. We
have included advanced mathematical analysis and modelling to determine the most important locations of cells
and signals needed to start and slow down tooth shedding. The synergistic research environment consists of the
PI who is a pediatric dentist and a developmental biologist, a mathematician specializing in mathematical biology,
an experienced technician who supports all molecular work, a bioinformatition who has worked on the gecko
genome with our lab and a new postdoc. The team is poised to make significant discoveries that can be
translated to treatments for failure of eruption and tooth loss in humans as well as other diseases such as
osteoporosis and osteoarthritis.
