Mammalian teeth

Mammalian teeth develop as ectodermal organs bearing many similarities to other such organs
like hair, feathers and mammary glands (Pispa and Thesleff, 2003). As such, teeth are
serially homologous and the developmental mechanisms that produce different tooth types in
an organized fashion have long been debated (Butler, 1939; Osborn, 1978; Weiss et al.,
1998). The positioning of teeth, their intricate and species-specific morphologies, timing of
development and regeneration imply stringent regulatory mechanisms of development and
make teeth a relevant and interesting model for several scientific disciplines. Basic problems
in developmental biology, including cell commitment, reciprocal tissue interactions, pattern
formation, positional information and development of complex morphologies may be approached
using teeth and dentitions as a model system (Weiss et al., 1998; Thesleff and
Nieminen, 2005). Teeth are useful for the research into evolutionary mechanisms because of
the species-specific morphologies based on adaptations of the tooth forms to the changing
habitat and lifestyle as well as because of resilience of teeth among the fossil record
(Jernvall, 1995; Jernvall et al., 2000). The replacement of teeth and the existence of continuously growing teeth offer a model for tissue regeneration and stem cell research (Huysseuneand Thesleff, 2004; Wang et al., 2007). Finally, the differentiation of the hard-tissue formingcells and the coupling of the differentiation into the morphogenesis may be studied to answerquestions on regulation of cell differentiation (Wang et al., 2004b; Thesleff and Nieminen,2005).

The strict genetic control of tooth development ensures that we all have a similar dentition
with anterior and posterior teeth of distinct shapes and times of eruption. However, despite
this similarity, all dentitions are unique and part of this individuality is created by variation
and features caused by genetic factors. Dental anthropologists have paid attention to various
morphological features with a hope that they could be used to clarify population history
(Dahlberg, 1945; Irish and Guatelli-Steinberg, 2003). The size and shape variation includes
all teeth but especially patterns of molar crowns (Dahlberg, 1945). The most salient features
involve abnormalities in tooth number. Developmental failure of one or more teeth, tooth
agenesis or hypodontia, is one of the most common anomalies in man, and depending on its
severity and location may be of aesthetic or clinical significance (Arte, 2001). Recently, a
connection between tooth agenesis and colorectal cancer was identified in a Finnish family,
suggesting that developmental anomalies of teeth may sometimes be signs of cancer predisposition (Lammi et al., 2004).

As part of a research which aims to understand the molecular mechanisms and genetic networks
regulating tooth development, a research project was started in 1992 to look for the
genetic factors that are responsible for tooth agenesis. During this project, different types of
familial tooth agenesis has been studied, and several gene defects and a new gene involved
in tooth agenesis identified. The original aim was to identify gene defects that underlie the
common type of tooth agenesis, incisor and premolar hypodontia. In this thesis, I present results
from studies into rare forms of tooth agenesis, and summarize results from genomewide
searches in several families with common incisor and premolar hypodontia.