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BMP4 signaling mediates Zeb family in developing mouse tooth

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Abstract

Tooth morphogenesis is regulated by sequential and reciprocal interaction between oral epithelium and neural-crest-derived ectomesenchyme. The interaction is controlled by various signal molecules such as bone morphogenetic protein (BMP), Hedgehog, fibroblast growth factor (FGF), and Wnt. Zeb family is known as a transcription factor, which is essential for neural development and neural-crest-derived tissues, whereas the role of the Zeb family in tooth development remains unclear. Therefore, this study aimed to investigate the expression profiles of Zeb1 and Zeb2 during craniofacial development focusing on mesenchyme of palate, hair follicle, and tooth germ from E12.5 to E16.5. In addition, we examined the interaction between Zeb family and BMP4 during tooth development. Both Zeb1 and Zeb2 were expressed at mesenchyme of the palate, hair follicle, and tooth germ throughout the stages. In the case of tooth germ at the cap stage, the expression of Zeb1 and Zeb2 was lost in epithelium-separated dental mesenchyme. However, the expression of Zeb1 and Zeb2 in the dental mesenchyme was recovered by Bmp4 signaling via BMP4-soaked bead and tissue recombination. Our results suggest that Zeb1 and Zeb2, which were mediated by BMP4, play an important role in neural-crest-derived craniofacial organ morphogenesis, such as tooth development.

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Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (R13-2003-013-05001-0).

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Authors and Affiliations

  1. Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Brain Korea 21 Project, Oral Science Research Center, College of Dentistry, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Korea

    Jeong-Oh Shin, Eun-Jung Kim, Kyoung-Won Cho, Eizo Nakagawa, Hyuk-Jae Kwon, Sung-Won Cho & Han-Sung Jung

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  1. Jeong-Oh Shin
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  2. Eun-Jung Kim
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  3. Kyoung-Won Cho
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  6. Sung-Won Cho
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Correspondence to Han-Sung Jung.

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Jeong-Oh Shin and Eun-Jung Kim contributed equally to this work.

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418_2012_930_MOESM1_ESM.tif

Supplementary Figure 1 (a-d) Expression of Zeb1 and Zeb2 in 24-h-cultured tooth germ with NOGGIN-soaked bead. (e-h) Expression patterns of Zeb1 and Zeb2 in 24-h culture tooth germ after treatment of dorsomorphin. Expression of Zeb1 and Zeb2 were disappeared after treatment NOGGIN and dorsomorphin to inhibit BMP signals. M, mesenchyme (TIFF 3574 kb)

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Shin, JO., Kim, EJ., Cho, KW. et al. BMP4 signaling mediates Zeb family in developing mouse tooth. Histochem Cell Biol 137, 791–800 (2012). https://doi.org/10.1007/s00418-012-0930-7

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