MSX2 in ameloblast cell fate and activity

Abstract

While many effectors have been identified in enamel matrix and cells via genetic studies, physiological networks underlying their expression levels and thus the natural spectrum of enamel thickness and degree of mineralization are now just emerging. Several transcription factors are candidates for enamel gene expression regulation and thus the control of enamel quality. Some of these factors, such as MSX2, are mainly confined to the dental epithelium. MSX2 homeoprotein controls several stages of the ameloblast life cycle. This chapter introduces MSX2 and its target genes in the ameloblast and provides an overview of knowledge regarding its effects in vivo in transgenic mouse models. Currently available in vitro data on the role of MSX2 as a transcription factor and its links to other players in ameloblast gene regulation are considered. MSX2 modulations are relevant to the interplay between developmental, hormonal and environmental pathways and in vivo investigations, notably in the rodent incisor, have provided insight into dental physiology. Indeed, in vivo models are particularly promising for investigating enamel formation and MSX2 function in ameloblast cell fate. MSX2 may be central to the temporal-spatial restriction of enamel protein production by the dental epithelium and thus regulation of enamel quality (thickness and mineralization level) under physiological and pathological conditions. Studies on MSX2 show that amelogenesis is not an isolated process but is part of the more general physiology of coordinated dental-bone complex growth.

Distorted Patterns of Dentinogenesis and Eruption in Msx2 Null Mutants

“…This is consistent with the known repressive transcriptional activity of Msx2 on mineralizing genes such as Bglap in bone 8 or Amelx and Calb1 in enamel. 4 Thus, dentinogenesis regulation by Msx2 might be secondary to particular cell-autonomous events targeting at least Dspp, Bglap, and Runx2. As previously demonstrated for amelogenesis under Msx2 inactivation, 10,12 initial dentinogenesis was not seriously affected, although there was some distortion of cusp patterns.…”

“…As previously demonstrated for amelogenesis under Msx2 inactivation, 10,12 initial dentinogenesis was not seriously affected, although there was some distortion of cusp patterns. 4,12 In contrast, at postnatal days 7 to 14, a pathologic osteodentin layer was deposited, characterized by entrapped odontoblasts able to secrete extracellular DSP but then disappearing, resulting in empty lacunae. After this transient event that simultaneously involved the entire odontoblast layer, the dentin exhibited hybrid features combining normal ordinary orthodentin morphology and sparse odontoblast inclusions reminiscent of tertiary osteodentinogenesis.…”

Bone resorption: an actor of dental and periodontal development?

“…Factors implicated in the cross-talk between epithelial and mesenchymal cells have been identified (for review Mitsiadis and Graf, 2009 ). Regarding later stages of tooth development, more precisely dental and periodontal histogenesis, the differentiation processes of mineralized tissue forming cells (namely amelogenesis, dentinogenesis and cementogenesis) have also been widely studied (Foster et al, 2007 ; Babajko et al, 2014 ; Bleicher, 2014 ). Pathologies associated with dysfunctions of these processes are nowadays well characterized as amelogenesis imperfecta and dentinogenesis imperfecta (Cobourne and Sharpe, 2013 ).…”

The effect of 1,25-dihydroxyvitamin D3 on MSX2 gene expression during tooth and alveolar bone development

“…On the other hand, other researches using MSX2 over-expression technique show that the increasing of amelogenin genes is associated with the thickening dental email. 19 Physiological functions of MSX2 on the alveolar bone and tooth development have also been analyzed using transgenic mice. In mice with mutant MSX2, there will be changes in the morphology of the teeth and periodontal tissues.…”