7 Retinoic Acid Signaling and the Zebrafish Dentition …
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layers very early in tooth germ formation (Knudsen 1965). Experiments with cultured
molar tooth germs began to narrow down more precisely the timing of VA sensitivity
in early tooth germ development and revealed that while ameloblasts/enamel are
sensitive to VA levels relatively late in tooth formation (Holloway and Mellanby 1961;
Biggerstaff et al. 1971), excess VA exposure during early tooth germ development has
a primary effect on the development and differentiation of odontoblasts and dentin
(Hurmerinta et al. 1980).
One in vivo study went so far as to suggest that excess RA was capable of transforming molar tooth morphological identity to that of an incisor (Kronmiller et al.
1995). However, because excess RA-induced molar cusp number reduction had been
reported previously (Mark et al. 1992), it was unclear whether the identity of molars
was changed to that of incisors after excess RA exposure, or whether the resulting
simple teeth represented molars with fewer cusps.
RA Levels Manipulation and Gene Expression During Early
Tooth Formation
In the last two decades of the twentieth century, research into how VA is involved in
controlling tooth development became more advanced and specific in two primary
ways: studies began to shift from altering dietary VA levels to more precise experiments that directly manipulated RA levels in the embryo. A major goal of the work
was to understand how RA signaling influences the genetic control of odontogenesis (Abbott and Pratt 1988; Kronmiller et al. 1992; Mark et al. 1995). Investigators
began to observe gene expression changes when RA levels were manipulated during early tooth formation and to learn how these changes might explain RA-related
dental phenotypic effects. For example, the expression of epidermal growth factor
(EGF) and its receptor were observed to be altered in mouse molar tooth germs
after exposure to high levels of RA, and this change to EGF activity was suggested
to be a possible pathway by which RA influences tooth development (Abbott and
Pratt 1988; Kronmiller et al. 1992). About this same time, RA receptors (RARs)
and cellular retinoic acid binding protein (CRABP) mRNA expression were found
to be present in developing rodent tooth germs (Mark et al. 1991; Bloch-Zupan et al.
1994), consistent with the idea of odontoblasts and ameloblasts directly responding
to RA signals during tooth development.
Thus, at the dawn of the twenty-first century, some basic roles of RA in tooth
formation were relatively well understood. However, with rise of the field of evolutionary developmental biology in the 1990s, the stage was perfectly set for the
next logical questions to be asked: are the roles for RA in tooth formation specific to
rodents or are they evolutionarily conserved with other vertebrates? Has RA signaling
contributed to the evolution of the different forms of teeth seen across vertebrates?
181
layers very early in tooth germ formation (Knudsen 1965). Experiments with cultured
molar tooth germs began to narrow down more precisely the timing of VA sensitivity
in early tooth germ development and revealed that while ameloblasts/enamel are
sensitive to VA levels relatively late in tooth formation (Holloway and Mellanby 1961;
Biggerstaff et al. 1971), excess VA exposure during early tooth germ development has
a primary effect on the development and differentiation of odontoblasts and dentin
(Hurmerinta et al. 1980).
One in vivo study went so far as to suggest that excess RA was capable of transforming molar tooth morphological identity to that of an incisor (Kronmiller et al.
1995). However, because excess RA-induced molar cusp number reduction had been
reported previously (Mark et al. 1992), it was unclear whether the identity of molars
was changed to that of incisors after excess RA exposure, or whether the resulting
simple teeth represented molars with fewer cusps.
RA Levels Manipulation and Gene Expression During Early
Tooth Formation
In the last two decades of the twentieth century, research into how VA is involved in
controlling tooth development became more advanced and specific in two primary
ways: studies began to shift from altering dietary VA levels to more precise experiments that directly manipulated RA levels in the embryo. A major goal of the work
was to understand how RA signaling influences the genetic control of odontogenesis (Abbott and Pratt 1988; Kronmiller et al. 1992; Mark et al. 1995). Investigators
began to observe gene expression changes when RA levels were manipulated during early tooth formation and to learn how these changes might explain RA-related
dental phenotypic effects. For example, the expression of epidermal growth factor
(EGF) and its receptor were observed to be altered in mouse molar tooth germs
after exposure to high levels of RA, and this change to EGF activity was suggested
to be a possible pathway by which RA influences tooth development (Abbott and
Pratt 1988; Kronmiller et al. 1992). About this same time, RA receptors (RARs)
and cellular retinoic acid binding protein (CRABP) mRNA expression were found
to be present in developing rodent tooth germs (Mark et al. 1991; Bloch-Zupan et al.
1994), consistent with the idea of odontoblasts and ameloblasts directly responding
to RA signals during tooth development.
Thus, at the dawn of the twenty-first century, some basic roles of RA in tooth
formation were relatively well understood. However, with rise of the field of evolutionary developmental biology in the 1990s, the stage was perfectly set for the
next logical questions to be asked: are the roles for RA in tooth formation specific to
rodents or are they evolutionarily conserved with other vertebrates? Has RA signaling
contributed to the evolution of the different forms of teeth seen across vertebrates?