Expression of new genes in vertebrate tooth development and p63 signaling

Abstract

Background p63 is an evolutionarily ancient transcription factor essential to vertebrate tooth development. Our recent gene expression screen comparing wild‐type and “toothless” p63−/− mouse embryos implicated in tooth development several new genes that we hypothesized act downstream of p63 in dental epithelium, where p63 is also expressed. Results Via in situ hybridization and immunohistochemistry, we probed mouse embryos (embryonic days 10.5‐14.5) and spotted gar fish embryos (14 days postfertilization) for these newly linked genes, Cbln1, Cldn23, Fermt1, Krt15, Pltp and Prss8, which were expressed in mouse and gar dental epithelium. Loss of p63 altered expression levels but not domains. Expression was comparable between murine upper and lower tooth organs, implying conserved gene functions in maxillary and mandibular dentitions. Our meta‐analysis of gene expression databases supported that these genes act within a p63‐driven gene regulatory network important to tooth development in mammals and more evolutionary ancient vertebrates (fish, amphibians). Conclusions Cbln1, Cldn23, Fermt1, Krt15, Pltp, and Prss8 were expressed in mouse and fish dental epithelium at placode, bud, and/or cap stages. We theorize that these genes participate in cell‐cell adhesion, cell polarity, and extracellular matrix signaling to support dental epithelium integrity, folding, and epithelial‐mesenchymal cross talk during tooth development.

Transcriptomic profiling of the adult reptilian dentition sheds light on the genes regulating indefinite tooth replacement

“…SHH was previously shown to be expressed in the embryonic leopard gecko enamel organ (Handrigan and Richman 2010). Cluster 6 cells expressed Fermt1 (Rostampour et al 2019), Irx1 (Yu et al 2017), Ednrb (Neuhaus and Byers 2007) and Itgb4 (Salmivirta et al 1996) all of which are expressed in the mouse enamel organ. Markers of fully functional ameloblasts were not identified in cluster 6, even though these genes were found in the bulk-RNA-seq data for developing teeth.…”

Novel Candidate Genes for Non-Syndromic Tooth Agenesis Identified Using Targeted Next-Generation Sequencing

“…Eight of these variants were identified in genes not previously associated with the ns-TA risk, including CHD7 (OMIM * 608892), CREBBP , EVC (OMIM * 604831), LEF1 (OMIM + 153245), ROR2 (OMIM * 602337), TBX22 (OMIM * 300307) and TP63 . Expression and functional studies have demonstrated that protein products of all these novel candidate genes play crucial roles during odontogenesis and craniofacial development [ 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Mice deficient in Lef1 , an essential epithelial survival factor in tooth morphogenesis, show arrested tooth development at the late bud stage before forming a mesenchymal dental papilla [ 20 , 27 ].…”

Tooth number abnormality: from bench to bedside

“…A gene regulatory network dominated by p63, which can regulate the adhesion, polarity and migration of odontogenic cells, may exist during the determination period of the dental-forming region. 35 Deficiencies of these transcription factors (Pitx2, Lef1 and P63) inhibit early tooth development, consequently leading to missing teeth. 33,[36][37][38][39][40] The developmental stage subsequent to the laminal stage is the placode stage (Fig.…”