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Epithelial Hedgehog signaling is essential for tooth patterning and enamel formation
Shanhui Gao1, Yuge Zhao1, Yan Wang1
1Zhejiang Key Laboratory of Organ Development and Regeneration, College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, 310036, People's Republic of China.
Bone
|July 28, 2026
Summary
Early Hedgehog signaling in dental epithelium is crucial for determining normal tooth number. Disrupting this pathway leads to supernumerary teeth and affects enamel formation by altering Wnt signaling.
Area of Science:
- Developmental Biology
- Genetics
- Oral Biology
Background:
- Supernumerary teeth are congenital anomalies linked to disrupted epithelial-mesenchymal interactions.
- Hedgehog signaling's precise role in tooth number determination is not fully understood.
Purpose of the Study:
- To investigate the temporal requirement of early epithelial Hedgehog signaling in tooth number determination.
- To elucidate the molecular mechanisms by which Hedgehog signaling influences odontogenesis.
Main Methods:
- Conditional deletion of Smoothened (Smo) in dental epithelium using Pitx2-Cre mouse model.
- Analysis of tooth morphology, cell proliferation (BrdU labeling), apoptosis, gene expression (in situ hybridization), and Wnt/β-catenin pathway activity.
- In vitro studies using Sonic Hedgehog (SHH) stimulation.
Main Results:
- Pitx2-Cre mediated Smo deletion resulted in two supernumerary mandibular incisors.
- Increased cell proliferation in the lingual cervical loop without altered apoptosis.
- Aberrant Wnt/β-catenin pathway activation with reduced Wnt inhibitors (Dkk1, Sostdc1) and increased Lef1.
- Downregulation of genes essential for ameloblast differentiation and dental patterning (Fgf3, Sp6, Dlx2, Msx2).
Conclusions:
- Epithelial Hedgehog signaling is essential during early odontogenesis for normal tooth patterning.
- This signaling pathway coordinates Wnt signaling and epithelial-mesenchymal communication.
- Hedgehog signaling also promotes ameloblast differentiation and enamel formation.
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