Homeobox code model of heterodont tooth in mammals revised

Abstract

Heterodonty is one of the hallmarks of mammals. It has been suggested that, homeobox genes, differentially expressed in the ectomesenchyme of the jaw primordium along the distal-proximal axis, would determine the tooth classes (homeobox code model) based on mouse studies. Because mouse has highly specialized tooth pattern lacking canine and premolars (dental formula: 1003/1003, for upper and lower jaws, respectively), it is unclear if the suggested model could be applied for mammals with all tooth classes, including human. We thus compared the homeobox code gene expressions in various mammals, such as opossum (5134/4134), ferret (3131/3132), as well as mouse. We found that Msx1 and BarX1 expression domains in the jaw primordium of the opossum and ferret embryos show a large overlap, but such overlap is small in mouse. Detailed analyses of gene expressions and subsequent morphogenesis of tooth germ in the opossum indicated that the Msx1 / BarX1 double-positive domain will correspond to the premolar region, and Alx3 -negative/ Msx1 -positive/ BarX1 -negative domain will correspond to canine. This study therefore provides a significant update of the homeobox code model in the mammalian heterodonty. We also show that the modulation of FGF-mediated Msx1 activation contributes to the variation in the proximal Msx1 expression among species.

Responses of Epibranchial Placodes to Disruptions of the FGF and BMP Signaling Pathways in Embryonic Mice

“…The underlying hypothesis is based on the fact that Fgf10 is upregulated in the branchial mesoderm by Fgf3 and Fgf8 (Alvarez et al, 2003;Wright and Mansour, 2003;Wright et al, 2004;Ladher et al, 2005;Aggarwal et al, 2006). FGF signaling in turn causes an upregulation of Msx1 in the branchial mesoderm during exactly the developmental period we are looking for (Wakamatsu et al, 2019; one embryonic day later: Chen et al, 1996). Exposure of our embryos to 0.5 µM of the pan-FGFR inhibitor PD173074 already leads to a discrete attenuation of the Msx1/2 signal (Supplementary Figure 2).…”

Domestic cat embryos reveal unique transcriptomes of developing incisor, canine, and premolar teeth

“…Previous studies of heterodont mammals including the house shrew ( S. murinus ) and the ferret ( M. furo ), as well as a marsupial, the short‐tailed opossum ( Monodelphis domestica ), demonstrated conservation of the homeobox code among placental mammals and marsupials and extended the homeobox code to include canine and premolar teeth. These studies showed that distinct combinatorial expression domains of Barx1, Msx1 , and Alx3 distinguish the incisor, canine, and premolar regions from one another (Miletich et al, 2011; Wakamatsu et al, 2019; Yamanaka et al, 2015). In addition to specifying regions within the dentition, expression of Barx1 in the least shrew ( C. parva) has been shown to correlate positively with the number of cusps on premolar and molar teeth; teeth with more cusps have higher Barx1 expression (Miletich et al, 2011).…”

“…Homeobox genes play critical roles in patterning the dentition into distinct regions in which different tooth classes form, known as the homeobox code (McCollum & Sharpe, 2001; Sharpe, 1995). Initially studied in incisors and molars of mice, the homeobox code has been extended to canine and premolar teeth in shrews ( Suncus murinus, Cryptotis parva ) and ferrets ( Mustela furo ) (Miletich et al, 2011; Wakamatsu et al, 2019; Yamanaka et al, 2015).…”

Bat teeth illuminate the diversification of mammalian tooth classes

“…On the other hand, developmental studies, largely based on morphological observations of the dental lamina of species 29 including the ferret 30 , shrew 31,32 , straw-colored fruit bat 33 , opossum ( 34 and personal observations), and this study reveal that lower premolars and molars tend to develop in opposite directions, and thereby support the hypothesis that premolars and molars are patterned through independent mechanisms. From a molecular perspective, some evidence suggests that the early patterning of the jaw is driven by a "homeobox-code" that divides the jaw into territories that determine tooth classes prior to bud development (reviewed in [35][36][37] ). While these results suggest that tooth class specification and/or determination might occur prior to placode induction, results of other studies suggest that this early code is not sufficient to establish tooth class identity.…”