Enamel-free teeth: Tbx1 deletion affects amelogenesis in rodent incisors

Abstract

TBX1 is a principal candidate gene for DiGeorge syndrome, a developmental anomaly that affects the heart, thymus, parathyroid, face, and teeth. A mouse model carrying a deletion in a functional region of the Tbx1 gene has been extensively used to study anomalies related to this syndrome. We have used the Tbx1 null mouse to understand the tooth phenotype reported in patients afflicted by DiGeorge syndrome. Because of the early lethality of the Tbx1−/− mice, we used long-term culture techniques that allow the unharmed growth of incisors until their full maturity. All cultured incisors of Tbx1−/− mice were hypoplastic and lacked enamel, while thorough histological examinations demonstrated the complete absence of ameloblasts. The absence of enamel is preceded by a decrease in proliferation of the ameloblast precursor cells and a reduction in amelogenin gene expression. The cervical loop area of the incisor, which contains the niche for the epithelial stem cells, was either severely reduced or completely missing in mutant incisors. In contrast, ectopic expression of Tbx1 was observed in incisors from mice with upregulated Fibroblast Growth Factor signalling and was closely linked to ectopic enamel formation and deposition in these incisors. These results demonstrate that Tbx1 is essential for the maintenance of ameloblast progenitor cells in rodent incisors and that its deletion results in the absence of enamel formation.

The Pitx2:miR-200c/141:noggin pathway regulates Bmp signaling and ameloblast differentiation

“…Sox2 and Tbx1 are dental stem cell markers as they are predominantly expressed in the CLs of the mouse incisors and/or affect progenitor cell proliferation (Cao et al, 2010a;Catón et al, 2009;Juuri et al, 2012;Mitsiadis et al, 2008). Other genes also mark the dental stem cells in the labial CL, such as Lgr5, Abcg2, Bmi1, Oct3/4 (Pou5f1 -Mouse Genome Informatics) and Yap1; however, their involvement in stem cell maintenance and proliferation is unknown (Li et al, 2011a;Suomalainen and Thesleff, 2010).…”

Whole-organ engineering with natural extracellular materials

“…Others have applied the roles of biglycan, and subsequent amelogenin expression, to nanofiber scaffolding to study enamel maturation [99][100][101]. Mouse knockout models have also elucidated the role of Tbx1 and enamel formation [102]. Still, further exploration of additional ECM molecules and corresponding spatial organization within the tooth are needed for the educated design of effective scaffolds for whole tooth tissue engineering.…”

Avances en La Genética De La Formación Dental: Una Revisión

“…En los molares, si el nudo de esmalte es demasiado pequeño, como se observa en ratones con mutaciones en Eda o Edrad, se afecta el plegado dental y la colocación de los nudos de esmalte secundarios, conduciendo a un molar con cúspides aplanadas. Por lo tanto, comprometer la señalización a partir del nudo de esmalte primario al modificar su tamaño o forma, implica cambios y defectos en la disposición de los nudos de esmalte secundarios en molares 22,25 .…”