Study of Pax6 mutant rat revealed the association between upper incisor formation and midface formation

Abstract

In this study, we investigated the process of supernumerary upper incisor formation in the Pax6 mutant rat, rSey 2 /rSey 2 , which exhibits a facial cleft between the medial nasal and maxillary processes. Histological investigation and epithelial labeling studies of wild type rat embryos indicated that the upper incisor develops by fusion of two primary dental placodes (PDPs) in the medial nasal process with a contribution from the epithelium of the maxillary process. In the rSey 2 /rSey 2 embryo, both PDPs are formed but they stay apart, then subsequently these PDPs independently develop into upper incisor tooth buds. In order to examine if the failure of the two placodes to fuse is due to the cleft between the maxillary and medial nasal processes, maxillary and medial nasal process fusion was inhibited with a barrier in wild type embryos. This resulted in the maintenance of the two distinct PDPs. These results demonstrate that fusion of the facial processes reduces the number of odontogenic placodes and is required to assemble all components at one site for rat upper incisor formation. The results also provide further insight into the mechanism of supernumerary incisor formation in human cleft lip conditions. Developmental Dynamics 235:2134 -2143, 2006.

Regulation of tooth number by fine-tuning levels of receptor-tyrosine kinase signaling

“…In Eda mutants, only very rare cases of side-by-side upper incisor duplication have been reported (Sofaer, 1969); we did not detect this phenotype during our observation of 60 heterozygous and 80 null Eda mutants in previous studies (Charles et al, 2009a;Charles et al, 2009b). Pax6 mutant rats, as Pax6-Sey mice, also exhibit supernumerary incisors, and it has been suggested that these incisors result from the total lack of fusion between two components of the epithelial incisor anlage separated by a cleft lip (Kriangkrai et al, 2006) and not from the secondary splitting of the incisor anlage as we have observed. Splitting of the incisor anlage might occur in nestin-cre/K5-lacZfl-smad7 mice, but the splitting seemed to be a transient event, as the two incisors were fused at their base (Klopcic et al, 2007).…”

<b>Analysis of the Association between Mesiodens and SNP Genotyping </b>

“…These previous reports suggest that activation of Wnt signaling by loss of function of its inhibitors leads to supernumerary teeth (20). Pax6, a paired homeobox protein transcription factor, is involved in neuronal and craniofacial development, including that of the optic and olfactory systems (14). In Pax6 rSey2/rSey2 mutant rats, histological analysis at E13.0 showed two dental placodes that were far apart, which was as opposed to those of wild-type embryos, and showed supernumerary incisors near the original upper incisor at E20 (14).…”

“…Pax6, a paired homeobox protein transcription factor, is involved in neuronal and craniofacial development, including that of the optic and olfactory systems (14). In Pax6 rSey2/rSey2 mutant rats, histological analysis at E13.0 showed two dental placodes that were far apart, which was as opposed to those of wild-type embryos, and showed supernumerary incisors near the original upper incisor at E20 (14). CEBPB (CCAAT/enhancer-binding protein beta)is a transcription factor that binds to consensus sequences and regulates the transcription of various genes involved in proliferation and differentiation; it is also suggested to be an important factor in osteogenesis and odontogenesis (35).…”

“…A variety of secreted molecules including wingless-type MMTV integration site family Correspondence to : Nao Kimura E-mail : mana14009@g.nihon-u.ac.jp (WNT), sonic hedgehog (Shh), bone morphogenetic proteins(BMPs), and fibroblast growth factors(FGFs)orchestrate development to regulate tooth shape, size, and number (10). In previous studies, sclerostin domain-containing protein 1(Sostdc1)-, LDL receptor-related protein 4(Lrp4) -, CCAAT/enhancer-binding protein beta (Cebpb) -, and adenomatous polyposis coli(Apc)-deficient mice, as well as paired box 6(Pax6)-mutant rats, presented with supernumerary teeth in the incisor area (11)(12)(13)(14)(15).…”

Pretreatment Effect of Folic Acid on 13-Cis-RA-Induced Cellular Damage of Developing Midfacial Processes in Cultured Rat Embryos

“…Interruption in the growth and merging of midfacial processes during E11-12 in rat embryos, may lead to facial defects such as cleft lip. The cleft lip is a merging failure between the MxPs and MNPs, while the median cleft lip is a merging failure of the MNPs into midline [4, 5]. …”