190
W. R. Jackman and Y. Gibert
Relevance
The influence of RA on tooth development in vertebrate species as divergent as mice
and zebrafish suggests a deep evolutionary conservation of this control. However, the
apparent independence of tooth development from RA signaling in more than one
other teleost species makes it clear that the evolutionary history of RA control of tooth
formation cannot be a simple one. Two possible scenarios out of many possibilities
are that RA was involved in tooth development at the origin of vertebrates, and then,
this involvement was lost in certain lineages, or, alternatively, RA signaling became
part of the tooth-making developmental process later on in certain groups, perhaps
independently.
Regarding the second possibility, one hypothesis that has been put forward is that
ancestral teleost fishes did not require RA for tooth formation, but used it instead
for other aspects of development, and that somewhere along the zebrafish lineage, a
requirement for RA was imposed upon developing teeth (Gibert et al. 2010). In other
words, somehow RA signaling became ‘hijacked’ into a tooth-forming developmental mechanism. A well-characterized example that illustrates how this evolutionary
switch of developmental control could work in principle can be found in the evolution
of wing spots in Drosophila species (Arnoult et al. 2013). Drosophila melanogaster
and the closely related Drosophila biarmipes both use the transcription factor distalless (Dll) as an essential controller of gene expression and morphology during wing
development. However, melanogaster wings are unpigmented whereas biarmipes
males have a conspicuous dark spot near the end of their wing in a location that overlaps with Dll expression, and in fact, requires Dll expression for spot formation. There
is evidence that some pigmentation genes in biarmipes have evolved Dll binding sites
in their enhancers, sites that are absent from their melanogaster counterparts, and
that Dll now controls not only morphology of the wing but spot formation as well.
Similarly, in the zebrafish lineage, if RA was being synthesized in the region of tooth
formation initially for some non-dental reason, it is possible to imagine that RAR
binding sites may have evolved in enhancers of important tooth-regulatory genes,
possibly resulting in the expression of these genes becoming more robust. Over time,
as other mutations accumulated in the zebrafish lineage, this initial RA ‘boost’ to
tooth development may have turned into a requirement. The expression patterns of
the RA synthesizing enzyme aldh1a2 between zebrafish, Mexican tetras, and medaka
are consistent with this idea, being highly expressed in the zebrafish tooth-forming
region and less so in the other species (Gibert et al. 2010; Seritrakul et al. 2012).
However, much more information regarding the transcriptional regulation of genes
in zebrafish and other species will be required to fully test this hypothesis, especially
the location and nature of developmental enhancers regulating genes involved in
odontogenesis, few of which are currently characterized.
W. R. Jackman and Y. Gibert
Relevance
The influence of RA on tooth development in vertebrate species as divergent as mice
and zebrafish suggests a deep evolutionary conservation of this control. However, the
apparent independence of tooth development from RA signaling in more than one
other teleost species makes it clear that the evolutionary history of RA control of tooth
formation cannot be a simple one. Two possible scenarios out of many possibilities
are that RA was involved in tooth development at the origin of vertebrates, and then,
this involvement was lost in certain lineages, or, alternatively, RA signaling became
part of the tooth-making developmental process later on in certain groups, perhaps
independently.
Regarding the second possibility, one hypothesis that has been put forward is that
ancestral teleost fishes did not require RA for tooth formation, but used it instead
for other aspects of development, and that somewhere along the zebrafish lineage, a
requirement for RA was imposed upon developing teeth (Gibert et al. 2010). In other
words, somehow RA signaling became ‘hijacked’ into a tooth-forming developmental mechanism. A well-characterized example that illustrates how this evolutionary
switch of developmental control could work in principle can be found in the evolution
of wing spots in Drosophila species (Arnoult et al. 2013). Drosophila melanogaster
and the closely related Drosophila biarmipes both use the transcription factor distalless (Dll) as an essential controller of gene expression and morphology during wing
development. However, melanogaster wings are unpigmented whereas biarmipes
males have a conspicuous dark spot near the end of their wing in a location that overlaps with Dll expression, and in fact, requires Dll expression for spot formation. There
is evidence that some pigmentation genes in biarmipes have evolved Dll binding sites
in their enhancers, sites that are absent from their melanogaster counterparts, and
that Dll now controls not only morphology of the wing but spot formation as well.
Similarly, in the zebrafish lineage, if RA was being synthesized in the region of tooth
formation initially for some non-dental reason, it is possible to imagine that RAR
binding sites may have evolved in enhancers of important tooth-regulatory genes,
possibly resulting in the expression of these genes becoming more robust. Over time,
as other mutations accumulated in the zebrafish lineage, this initial RA ‘boost’ to
tooth development may have turned into a requirement. The expression patterns of
the RA synthesizing enzyme aldh1a2 between zebrafish, Mexican tetras, and medaka
are consistent with this idea, being highly expressed in the zebrafish tooth-forming
region and less so in the other species (Gibert et al. 2010; Seritrakul et al. 2012).
However, much more information regarding the transcriptional regulation of genes
in zebrafish and other species will be required to fully test this hypothesis, especially
the location and nature of developmental enhancers regulating genes involved in
odontogenesis, few of which are currently characterized.