Abstract
Mammalian tooth crown formation has long served as a model for investigating how patterning and morphogenesis are orchestrated during development. However, the mechanism underlying root patterning and morphogenesis remains poorly understood. In this study, we find that Lhx6 labels a subpopulation of root progenitor cells in the apical dental mesenchyme, which is closely associated with furcation development. Loss of Lhx6 leads to furcation and root number defects, indicating that Lhx6 is a key root patterning regulator. Among the multiple cellular events regulated by Lhx6 is the odontoblast fate commitment of progenitor cells, which it controls in a cell-autonomous manner. Specifically, Lhx6 loss leads to elevated expression of the Wnt antagonist Sfrp2 and down-regulation of Wnt signaling in the furcation region, while overactivation of Wnt signaling in Lhx6+ progenitor cells partially restore the furcation defects in Lhx6-/- mice. Collectively, our findings have important implications for understanding organ morphogenesis and future strategies for tooth root regeneration.
Highlights
Teeth are biomineralized organs in the oral cavity that support physiological functions including eating, pronunciation, and facial esthetics
The number of the tooth roots varies in a manner that is finely tailored to the physiological function of each tooth type
We divided the developing tooth root into two parts: the furcation development region (FDR) in the middle and the non-furcation development region (NFDR) where root elongation occurs on either side (Fig 1A)
Summary
Teeth are biomineralized organs in the oral cavity that support physiological functions including eating, pronunciation, and facial esthetics. Morphological features of roots, including both their length and number, vary across the mammalian dentition. Investigating how root morphology is patterned is of significance for several reasons. Uncovering the mechanisms by which root morphology is regulated provides clues that may reveal common principles of developmental biology [1]. A comprehensive understanding of how root morphology is determined serves as a prerequisite for tooth root regeneration, because root shape and number are tightly connected to the unique physiological function of each particular type of tooth. Tooth root traits provide crucial evidence that elucidates the evolutionary history of hominins [2,3,4]. The molecular mechanism that regulates tooth root patterning and morphogenesis remains largely unclear [5]
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