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W. R. Jackman and Y. Gibert
to tooth formation, using the logic that evolutionary conservation might be the rule
instead of the exception, and this approach paid off quickly. For example, zebrafish
homologs of transcription factors, such as Pitx2 and Dlx2, that were known to be
expressed very early in mouse tooth formation, were found to have extremely similar
expression patterns in the developing odontoblasts and ameloblasts of zebrafish tooth
germs (Jackman et al. 2004). Cell signaling also began to be studied at this time,
with fibroblast growth factor (FGF) ligands found to be expressed in developing
zebrafish tooth germs, and chemical and genetic inhibition of these ligands shown
to interfere with normal tooth formation, indicating an FGF signaling requirement
for proper tooth formation (Jackman et al. 2004). At this same time, new genes that
hadn’t previously been studied in mammals were also being discovered to have a
role in zebrafish tooth development (e.g. Laurenti et al. 2004), and developmental
gene expression began to be examined in other fish species as well, establishing a
rich evolutionary comparative context for the work (Fraser et al. 2004; Stock et al.
2006).
The picture that emerged from these first studies of developing fish tooth germ
anatomy, gene expression, and gene function was largely one of homology and conservation across vertebrates, with the odontoblast and ameloblast cell layers playing
important roles in tooth formation and with a large degree of gene expression conservation as these layers form (Fraser et al. 2004; Jackman et al. 2004). For example,
the sonic hedgehog (Shh) cell signaling ligand, which was known to be expressed
in a subset of cells in the ameloblast of developing mammalian teeth, was found to
be expressed in a similar pattern in developing zebrafish and other bony fish. More
recently, Shh has been found in sharks as well (Fraser et al. 2004; Stock et al. 2006;
Rasch et al. 2016). Experiments chemically blocking Shh function support the idea
that Shh has a shared, essential function across vertebrates. Bmp4 and the transcription factor Pax9 have also been found to be conserved in developing odontoblast
cells (Wise and Stock 2006; Rasch et al. 2016). While there are many similarities
between species, some differences are also found, such as an apparent lack of Pax9
expression in developing zebrafish teeth (Jackman et al. 2004). Nevertheless, in the
overall context of evolutionary conservation, differences can be as interesting as similarities, as changes to tooth development may help explain how teeth have evolved
differently in diverse vertebrate groups.
Cranial Neural Crest Cells and Zebrafish Teeth
Odontoblasts in all vertebrates are thought to arise during embryonic development
from cranial neural crest (CNC) cells, a group of ectodermal cells that migrate out
of the developing neural tube and differentiate into a wide array of other cell types,
including peripheral neurons, glia, pigment cells, chondrocytes (Green et al. 2015),
and zebrafish teeth (Jackman et al. 2004; Seritrakul et al. 2012). CNC cells are thought
to have evolved, or at least to have become greatly elaborated, in early vertebrates
(Jeffery et al. 2008). CNC development has been extensively studied in chicken and
W. R. Jackman and Y. Gibert
to tooth formation, using the logic that evolutionary conservation might be the rule
instead of the exception, and this approach paid off quickly. For example, zebrafish
homologs of transcription factors, such as Pitx2 and Dlx2, that were known to be
expressed very early in mouse tooth formation, were found to have extremely similar
expression patterns in the developing odontoblasts and ameloblasts of zebrafish tooth
germs (Jackman et al. 2004). Cell signaling also began to be studied at this time,
with fibroblast growth factor (FGF) ligands found to be expressed in developing
zebrafish tooth germs, and chemical and genetic inhibition of these ligands shown
to interfere with normal tooth formation, indicating an FGF signaling requirement
for proper tooth formation (Jackman et al. 2004). At this same time, new genes that
hadn’t previously been studied in mammals were also being discovered to have a
role in zebrafish tooth development (e.g. Laurenti et al. 2004), and developmental
gene expression began to be examined in other fish species as well, establishing a
rich evolutionary comparative context for the work (Fraser et al. 2004; Stock et al.
2006).
The picture that emerged from these first studies of developing fish tooth germ
anatomy, gene expression, and gene function was largely one of homology and conservation across vertebrates, with the odontoblast and ameloblast cell layers playing
important roles in tooth formation and with a large degree of gene expression conservation as these layers form (Fraser et al. 2004; Jackman et al. 2004). For example,
the sonic hedgehog (Shh) cell signaling ligand, which was known to be expressed
in a subset of cells in the ameloblast of developing mammalian teeth, was found to
be expressed in a similar pattern in developing zebrafish and other bony fish. More
recently, Shh has been found in sharks as well (Fraser et al. 2004; Stock et al. 2006;
Rasch et al. 2016). Experiments chemically blocking Shh function support the idea
that Shh has a shared, essential function across vertebrates. Bmp4 and the transcription factor Pax9 have also been found to be conserved in developing odontoblast
cells (Wise and Stock 2006; Rasch et al. 2016). While there are many similarities
between species, some differences are also found, such as an apparent lack of Pax9
expression in developing zebrafish teeth (Jackman et al. 2004). Nevertheless, in the
overall context of evolutionary conservation, differences can be as interesting as similarities, as changes to tooth development may help explain how teeth have evolved
differently in diverse vertebrate groups.
Cranial Neural Crest Cells and Zebrafish Teeth
Odontoblasts in all vertebrates are thought to arise during embryonic development
from cranial neural crest (CNC) cells, a group of ectodermal cells that migrate out
of the developing neural tube and differentiate into a wide array of other cell types,
including peripheral neurons, glia, pigment cells, chondrocytes (Green et al. 2015),
and zebrafish teeth (Jackman et al. 2004; Seritrakul et al. 2012). CNC cells are thought
to have evolved, or at least to have become greatly elaborated, in early vertebrates
(Jeffery et al. 2008). CNC development has been extensively studied in chicken and