Abstract
Abstract
Background
Sclerostin domain‐containing 1 (SOSTDC1) deficiency enhances BMP and Wnt signaling, causing supernumerary teeth formation. Competing hypotheses of this formation at different sites have been proposed, and the underlying molecular mechanisms and cell types remain poorly understood.
Results
We examined
Sostdc1
knockout effects on spatiotemporal expression of Wnt pathway genes in developing maxillary incisors. In wild type mice, we observed an inverse spatiotemporal expression of
Sostdc1
and
Wnt10a
. The knockout caused ectopic expression of
Wnt10a, Wnt6
,
Lrp4
,
Dkk1
, and
Sost
and produced a distinct subpopulation of mesenchymal cells. Their spatial transcriptomic analysis and validation of marker genes by in situ mRNA hybridization suggested an unexpected mix of osteogenic and odontogenic differentiation. These cells evolved at the rudimentary labial incisor outgrowth at ~E15.5. At E16.5, their population expanded toward the lingual cervical loop, where a separate supernumerary tooth formed at E17.5.
Conclusion
The loss of Wnt and BMP signaling inhibition by SOSTDC1 causes aberrant mixed osteogenic and odontogenic differentiation of mesenchymal cells, contributing first to the labial outgrowth and then to the formation of the lingual supernumerary tooth. We hypothesize that this aberrant differentiation underlies the pathology, yet its direct functional role in the supernumerary tooth formation remains to be established.