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Using Confocal Analysis of Xenopus laevis to Investigate Modulators of Wnt and Shh Morphogen Gradients
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MSX1 Drives Tooth Morphogenesis Through Controlling Wnt Signaling Activity.
J-M Lee1, C Qin2,3, O H Chai2,4
1Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York, Buffalo, NY, USA.
Journal of Dental Research
|February 4, 2022
Summary
Homeobox transcription factor Msx1 controls tooth development by regulating Wnt signaling antagonists Dkk2 and Sostdc1. Genetic inactivation of these antagonists rescues tooth agenesis in Msx1-deficient mice, revealing their crucial role in early tooth morphogenesis.
Area of Science:
- Developmental Biology
- Genetics
- Oral Biology
Background:
- Tooth agenesis is a common human birth defect impacting early tooth development.
- The homeobox transcription factor Msx1 and Wnt signaling are critical for tooth morphogenesis.
- Msx1 is known to regulate Wnt signaling antagonists like Dkk2 and Sfrp2.
Purpose of the Study:
- To investigate the role of Sostdc1/Wise, a Wnt antagonist, in Msx1-dependent tooth development.
- To elucidate the interplay between Msx1, Dkk2, and Sostdc1 in regulating early tooth morphogenesis.
- To determine the rescue potential of modulating Wnt antagonists in Msx1-deficient mice.
Main Methods:
- Utilized Msx1-deficient mouse models (Msx1-/-).
- Generated and analyzed genetic inactivation models: Sostdc1-/-, Msx1-/-;Sostdc1-/-, Msx1-/-;Dkk2-/-, and Msx1-/-;Dkk2-/-;Sostdc1-/-.
- Examined tooth germ development and morphogenesis at the bud-to-cap transition stage.
Main Results:
- Genetic inactivation of Sostdc1 partially rescued maxillary molar development in Msx1-/- mice.
- Msx1-/-;Dkk2-/- double mutants showed rescued maxillary molar morphogenesis.
- Msx1-/-;Dkk2-/-;Sostdc1-/- triple mutants exhibited complete rescue of both maxillary and mandibular molar development.
- Ectopic Dkk2 expression was observed in Msx1-/- embryos, suggesting Msx1 controls Dkk2 expression.
Conclusions:
- Msx1 is essential for controlling Dkk2 expression during the bud-to-cap transition in tooth development.
- Dkk2 and Sostdc1, as Wnt signaling modulators, play critical roles in the Msx1-dependent odontogenic pathway.
- Targeting these Wnt antagonists offers a potential therapeutic strategy for tooth agenesis.
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