During the cap stage and early bell stage, the expressions of Fgf3, Fgf10, and Fgfr2 are detectable in the mesenchyme.
In addition, the expressions of Fgf3 and Fgf10 are found in the mesenchyme, and their expression is negatively regulated when dental papilla cells undergo differentiation to become odontoblasts [63, 106].
It has also been reported that increased [beta]-catenin signaling is related to the fate of dental mesenchymal cells, while FGF3 can sustain the odontogenic fate of incisor mesenchymal cells by down-regulating intracellular [beta]-catenin signaling .
In the mesenchyme, the expression of Fgf3 is maintained by FGF4 and FGF9, which are detected to be highly expressed in the pEK and sEK [63, 66].
FGF20 is another member of the FGF9 family, and its expression is found in the anterior bud of the lamina and the EK, along with the expressions of Fgf3, Fgf4, Fgf9, and Fgf15 [65, 66, 123].
During incisor development, an overlapping expression of Fgf3 and Fgf10 is initially detected in the dental papilla and is maintained through E14 in the incisor bud .
As a result, ectopic mesenchymal expressions of Fgf3 and Fgf10 as well as lingual ameloblast formation were observed .
However, an abnormal expression of Fgf3 has been found in the lingual side of the mesenchyme in [Spry2.sup.+/-];[Spry4.sup.-/-] mice, which in turn leads to the formation of TA cells and ameloblasts without lingual E-cadherin [93, 127].
The symmetrical expression of BMP4 occurs throughout the mesenchyme and suppresses the expression of Fgf3 indirectly in the lingual mesenchyme.
In addition, compound heterozygous or homozygous FGF3 mutations cause congenital deafness with labyrinthine aplasia, microtia, and microdontia (LAMM; OMIM no.
Riley, "Zebrafish fgf3 and fgf8 encode redundant functions required for otic placode induction," Developmental Biology, vol.