7 Retinoic Acid Signaling and the Zebrafish Dentition …
191
The Future
Further Explorations of the Role of RA in the Origin of Dental
Diversity
From the long history of study of RA in tooth formation, it is clear that RA signaling
is deeply entwined in vertebrate tooth development and evolution. However, despite
numerous investigations into its roles, there are still many questions to answer before
there is a complete understanding of RA in these processes. On the developmental
side, more needs to be learned about the exact cells that are responding to RA
during tooth development, and more precisely, how the cells respond by altering their
gene expression patterns and behaviors. Regarding evolution, a greater diversity of
vertebrate species needs to be examined to gain a better notion of how RA signaling
and odontogenesis have changed over time.
One promising avenue to a better understanding of RA function during tooth development will be to study RA signaling in context with other cell signaling pathways,
such as the FGF pathway. This kind of approach has been taken in an investigation
of the developmental origin of tooth morphology in mouse, asking the broad question of how mammals have evolved complex changes to molar cusp number and
shape, despite the fact that these processes seem very well buffered from change
during development (Harjunmaa et al. 2012). The most prominent finding of this
study was that in order to significantly alter molar tooth morphology in a way that
increased its complexity, as measured by cusp number, the activity of multiple cell
signaling pathways needed to be simultaneously manipulated at early stages of tooth
formation. This result highlights the fact that cell signaling pathways, such as RA
and FGF, are not operating in isolation, but that some cells involved in tooth formation may respond differently as a consequence of simultaneous signaling or changes
to signaling. Investigating how simultaneous changes to each pathway might affect
odontoblasts and ameloblasts as they are developing and forming teeth will help
pinpoint which aspects of cell behavior are under RA control, even in the complex
environment of the developing embryo.
Another promising area will be to explore similarities and differences between
zebrafish dentition and the dentition of other species (Fig. 7.6) (Seritrakul et al. 2012).
Does increasing RA signaling in zebrafish somehow trigger a dormant, more elaborate tooth developmental program similar to that of an ancestor? As mentioned above,
one problem that needs to be overcome is the conflicting data regarding the importance of RA in tooth development between different vertebrate lineages. Altering
RA signaling in zebrafish produces profound changes to tooth formation, but similar
experiments in some of the other teleost fish species examined thus far seem to have
little effect on odontogenesis. In contrast, tooth development in both zebrafish and
mammals, very distantly related vertebrate groups, both respond strongly to alterations in RA levels. These seemingly conflicting results lead to several questions.
Have changes to RA signaling been especially important in Cypriniform evolution,
191
The Future
Further Explorations of the Role of RA in the Origin of Dental
Diversity
From the long history of study of RA in tooth formation, it is clear that RA signaling
is deeply entwined in vertebrate tooth development and evolution. However, despite
numerous investigations into its roles, there are still many questions to answer before
there is a complete understanding of RA in these processes. On the developmental
side, more needs to be learned about the exact cells that are responding to RA
during tooth development, and more precisely, how the cells respond by altering their
gene expression patterns and behaviors. Regarding evolution, a greater diversity of
vertebrate species needs to be examined to gain a better notion of how RA signaling
and odontogenesis have changed over time.
One promising avenue to a better understanding of RA function during tooth development will be to study RA signaling in context with other cell signaling pathways,
such as the FGF pathway. This kind of approach has been taken in an investigation
of the developmental origin of tooth morphology in mouse, asking the broad question of how mammals have evolved complex changes to molar cusp number and
shape, despite the fact that these processes seem very well buffered from change
during development (Harjunmaa et al. 2012). The most prominent finding of this
study was that in order to significantly alter molar tooth morphology in a way that
increased its complexity, as measured by cusp number, the activity of multiple cell
signaling pathways needed to be simultaneously manipulated at early stages of tooth
formation. This result highlights the fact that cell signaling pathways, such as RA
and FGF, are not operating in isolation, but that some cells involved in tooth formation may respond differently as a consequence of simultaneous signaling or changes
to signaling. Investigating how simultaneous changes to each pathway might affect
odontoblasts and ameloblasts as they are developing and forming teeth will help
pinpoint which aspects of cell behavior are under RA control, even in the complex
environment of the developing embryo.
Another promising area will be to explore similarities and differences between
zebrafish dentition and the dentition of other species (Fig. 7.6) (Seritrakul et al. 2012).
Does increasing RA signaling in zebrafish somehow trigger a dormant, more elaborate tooth developmental program similar to that of an ancestor? As mentioned above,
one problem that needs to be overcome is the conflicting data regarding the importance of RA in tooth development between different vertebrate lineages. Altering
RA signaling in zebrafish produces profound changes to tooth formation, but similar
experiments in some of the other teleost fish species examined thus far seem to have
little effect on odontogenesis. In contrast, tooth development in both zebrafish and
mammals, very distantly related vertebrate groups, both respond strongly to alterations in RA levels. These seemingly conflicting results lead to several questions.
Have changes to RA signaling been especially important in Cypriniform evolution,