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Roles of Bmp4 during tooth morphogenesis and sequential tooth formation
Shihai Jia1, Jing Zhou, Yang Gao
1Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Development (Cambridge, England)
|December 20, 2012
Summary
Bone morphogenetic protein 4 (Bmp4) signaling is crucial for tooth development, suppressing inhibitors like Dkk2 and Osr2. It works with Msx1 to promote tooth formation and regulate sequential tooth development.
Area of Science:
- Developmental Biology
- Molecular Biology
- Genetics
Background:
- Bone morphogenetic protein 4 (Bmp4) is implicated as a key Msx1-dependent signal in tooth morphogenesis.
- Msx1(-/-) mice exhibit tooth germ arrest at the bud stage.
Purpose of the Study:
- To investigate the role of Bmp4 in tooth development and its interaction with Msx1 and Osr2.
- To elucidate the mechanisms underlying differential maxillary and mandibular molar development.
Main Methods:
- Neural crest-specific gene inactivation of Bmp4 in Bmp4(f/f);Wnt1Cre mice.
- Analysis of tooth germ development in wild-type and mutant embryos.
- Gene expression analysis of Osr2, Msx1, Dkk2, and Wif1.
Main Results:
- Depletion of Bmp4 caused mandibular molar arrest but allowed maxillary molar and incisor development.
- Osr2 expression was upregulated in Bmp4-deficient molar mesenchyme.
- Msx1 heterozygosity exacerbated defects, while Osr2 heterozygosity partially rescued mandibular molar defects.
- Compound mutants showed supernumerary tooth formation with reduced Msx1 expression.
- Dkk2 expression was upregulated in Bmp4-deficient molar mesenchyme, correlating with phenotypic differences.
Conclusions:
- Bmp4 signaling suppresses tooth developmental inhibitors (Dkk2, Osr2) in the mesenchyme.
- Bmp4 synergizes with Msx1 to activate mesenchymal odontogenic potential for tooth morphogenesis.
- Bmp4 plays a critical role in regulating sequential tooth formation and regional tooth development.
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