Specificity protein 7 is not essential for tooth morphogenesis

Abstract

Tooth formation is a multifaceted process involving numerous interactions between oral epithelium and neural crest derived ecto-mesenchyme from morphogenesis to cytodifferentiation. The precise molecular regulator that drives the cyto-differentiation and dynamic cross-talk between the two cell types has yet to be fully understood. Runx2 along with its downstream target Sp7 are essential transcription factors for development of the mineralizing cell types. Global knockout of the Runx2 gene results in an arrest of tooth morphogenesis at the late bud stage. Like Runx2, Sp7-null mutants exhibit peri-natal lethality and are completely devoid of alveolar bone. However, the role of Sp7 in tooth development remains elusive. Here, we report the effects of Sp7 deletion on tooth formation. Surprisingly, tooth morphogenesis progresses normally until the mid bell stage in Sp7-homozygous mutants. Incisors and multi-cusped first and second molars were noted in both littermates. Thus, formation of alveolar bone is not a prerequisite for tooth morphogenesis. Tooth organs of Sp7-null however, were significantly smaller in size when compared to WT. Differentiation of both ameloblasts and odontoblasts was disrupted in Sp7-null mice. Only premature and disorganized ameloblasts and odontoblasts were noted in mutant mice. These data indicate that Sp7 is not required for tooth morphogenesis but is obligatory for the functional maturation of both ameloblasts and odontoblasts.

Response to Letter to the Editor, “Osterix Regulates Tooth Root Formation in a Site-specific Manner”

“…In this context, it is notable that "rootless" teeth are produced without crown defect in the tissue-specific β-catenin inactivation mice (Kim et al 2013).We also examined tooth phenotype of Osterix null newborn mice (Appendix Fig.). Although crown morphogenesis was normal, differentiation of both odontoblasts and ameloblasts was disrupted as reported previously (Clarke et al 2014). In addition, Osterix is known to be short-lived protein, easily sumoylated and ubiquitinated (Hosoya et al 2013;Peng et al 2013).…”

Trps1 transcription factor regulates mineralization of dental tissues and proliferation of tooth organ cells

“…4). Considering that both Runx2 and Osx are highly expressed in dental mesenchyme and their expression becomes more restricted as tooth development progresses through the cytodifferentiation [27][28][29] , their expanded expression in the Trps1 −/− pulp may be indicative of delayed tooth development.…”