Abstract
In tooth bioengineering for replacement therapy of missing teeth, the utilized cells must possess an inductive signal-forming ability to initiate odontogenesis. This ability is called odontogenic potential. In mice, the odontogenic potential signal is known to be translocated from the epithelium to the mesenchyme at the early bud stage in the developing molar tooth germ. However, the identity of the molecular constituents of this process remains unclear. The purpose of this study is to determine the molecular identity of odontogenic potential and to provide a new perspective in the field of tooth development research. In this study, whole transcriptome profiles of the mouse molar tooth germ epithelium and mesenchyme were investigated using the RNA sequencing (RNA-seq) technique. The analyzed transcriptomes corresponded to two developmental stages, embryonic day 11.5 (E11.5) and 14.5 (E14.5), which represent the odontogenic potential shifts. We identified differentially expressed genes (DEGs), which were specifically overexpressed in both the E11.5 epithelium and E14.5 mesenchyme, but not expressed in their respective counterparts. Of the 55 DEGs identified, the top three most expressed transcription factor genes (transcription factor AP-2 beta isoform 3 [TFAP2B], developing brain homeobox protein 2 [DBX2], and insulin gene enhancer protein ISL-1 [ISL1]) and three tooth development-related genes (transcription factor HES-5 [HES5], platelet-derived growth factor D precursor [PDGFD], semaphrin-3A precursor [SEMA3A]) were selected and validated by quantitative RT-PCR. Using immunofluorescence staining, the TFAP2B protein expression was found to be localized only at the E11.5 epithelium and E14.5 mesenchyme. Thus, our empirical findings in the present study may provide a new perspective into the characterization of the molecules responsible for the odontogenic potential and may have an implication in the cell-based whole tooth regeneration strategy.
Highlights
In vertebrates, organogenesis depends on a well-organized series of induction phenomena, especially on the interactions between the epithelium and mesenchyme, including various signaling pathways [1]
The odontogenic potential signal is known to be translocated from the epithelium to the mesenchyme at the early bud stage in the developing molar tooth germ
To investigate the gene expression profile changes during embryonic odontogenesis, we collected both dental epithelial and mesenchymal tissues from the lower molar tooth germ of E11.5 and E14.5 mice, and sequenced an average of 75 million raw reads, which provide a sufficient depth of coverage for detecting the most expressed genes in the genome [21]
Summary
Organogenesis depends on a well-organized series of induction phenomena, especially on the interactions between the epithelium and mesenchyme, including various signaling pathways [1]. Odontogenesis is a complex process that involves reciprocal induction between the ectodermal epithelium and mesenchyme originated from the neural crest [2]. The odontogenic potential first appears on the dental lamina stage, corresponding to mouse embryonic day 10.5, initially at the dental epithelium. The previously mentioned events were validated by experiments that induced odontogenesis by recombining epithelium or mesenchyme possessing odontogenic potential with non-dental cells, such as embryonic stem cells, bone marrow-derived cells, keratinocytes, gingival epithelial cells, and hair follicle dermal papilla cells [9,10,11,12,13]. It was reported that the odontogenic potential was preserved in the epithelium and mesenchyme of the human tooth germ, its conversion issuing time was different [8]
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