Role of Dlx-1 and Dlx-2 genes in patterning of the murine dentition

Abstract

The molecular events of odontogenic induction are beginning to be elucidated, but until now nothing was known about the molecular basis of the patterning of the dentition. A role for Dlx-1 and Dlx-2 genes in patterning of the dentition has been proposed with the genes envisaged as participating in an ‘odontogenic homeobox gene code’ by specifying molar development. This proposal was based on the restricted expression of the genes in molar ectomesenchyme derived from cranial neural crest cells prior to tooth initiation. Mice with targeted null mutations of both Dlx-1 and Dlx-2 homeobox genes do not develop maxillary molar teeth but incisors and mandibular molars are normal. We have carried out heterologous recombinations between mutant and wild-type maxillary epithelium and mesenchyme and show that the ectomesenchyme underlying the maxillary molar epithelium has lost its odontogenic potential. Using molecular markers of branchial arch neural crest (Barx1) and commitment to chondrogenic differentiation (Sox9), we show that this population alters its fate from odontogenic to become chondrogenic. These results provide evidence that a subpopulation of cranial neural crest is specified as odontogenic by Dlx-1 and Dlx-2 genes. Loss of function of these genes results in reprogramming of this population of ectomesenchyme cells into chondrocytes. This is the first indication that the development of different shaped teeth at different positions in the jaws is determined by independent genetic pathways.

MMP-20 Is Predominately a Tooth-Specific Enzyme with a Deep Catalytic Pocket that Hydrolyzes Type V Collagen

“…The HOMF family is composed of homeodomain transcription factors, including Dlx and Msx, both of which are important factors necessary for tooth development. Deletion of Dlx1 and Dlx2 from the mouse genome results in the loss of maxillary molars (45), whereas the expression of Dlx5 and Dlx6 compensates for this loss and allows molar development in the mandibles of these animals (reviewed in ref 46). A Dlx3 mutation was demonstrated to cause defective dental enamel (amelogenesis imperfecta) and enlarged pulp chambers (taurodontism) in humans (47).…”

“…Biochemistry, Vol. 45 was previously identified as an MMP-20 substrate (41), so it served as the positive control. SDS-PAGE analysis demonstrated that type V, but not type III, collagen was cleaved by MMP-20 (Figure 5, top panel).…”

Near-chromosomal de novo assembly of Bengal tiger genome reveals genetic hallmarks of apex-predation

“…In addition to Fgf genes , we also identified Matrix metalloproteinase-20 ( Mmp-20 ) that has been shown to be involved in tooth development ( Figure 2b ; Supplementary Tables 1k and 1m ). (Thomas and Sharpe, 1998; Thomas et al, 1997).…”

“…In addition to Fgf genes, we also identified Matrix metalloproteinase-20 (Mmp-20) that has been shown to be involved in tooth development (Figure 2b; Supplementary Tables 1k and 1m). [45,46]. The retractable sharp tiger claws are an important tiger adaptation critical for predation.…”

Role of Cell Death in Cellular Processes During Odontogenesis

“…A different member of the homeodomain family of transcription factors, Distal-less homeobox2 (Dlx2), is expressed in the cementum layer and targeted null mutation of this gene cause disruption of tooth development in mice (Thomas et al, 1997). A transgenic mouse overexpressing Dlx2 in neural crest cells demonstrates tooth abnormalities like incisor crossbite, shortened tooth roots, increased cementum deposition, periodontal ligament disorganization and osteoporotic alveolar bone (Dai et al, 2017).…”