Shh signaling is essential for rugae morphogenesis in mice |
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Authors: | Jong-Min Lee Seita Miyazawa Jeong-Oh Shin Hyuk-Jae Kwon Dae-Woon Kang Byung-Jai Choi Jae-Ho Lee Shigeru Kondo Sung-Won Cho Han-Sung Jung |
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Institution: | (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 Center of Biotechnology, Yonsei University, 134 Shinchon-Dong, Seodaemoon-Gu, Seoul, 120-752, Korea;(2) Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan;(3) Department of Pediatric Dentistry, Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Korea |
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Abstract: | Palatal ridges, or rugae palatinae, are corrugated structures observed in the hard palate region. They are found in most mammalian
species, but their number and arrangement are species-specific. Nine palatal rugae are found in the mouse secondary palate.
Previous studies have shown that epithelial Shh signaling in the palatal ridge plays an important role during rugae development. Moreover, Wnt family members, including
LEF1, play a functional role in orofacial morphogenesis. To explore the function of Shh during rugae development, we utilized the maternal transfer of 5E1 (anti-Shh antibody) to mouse embryos. 5E1 induced abnormal
rugae patterning characterized by a spotted shape of palatal ridge rather than a stripe. The expression patterns of Shh and Shh-related genes, Sostdc1, Lef1 and Ptch1, were disrupted following 5E1 injection. Moreover, rugae-specific cell proliferation and inter-rugae-specific apoptosis were
affected by inhibition of Shh signaling. We hypothesize that the altered gene expression patterns and the change in molecular events caused by the inhibition
of Shh signaling may have induced abnormal rugae patterning. Furthermore, we propose a reaction–diffusion model generated by Wnt,
Shh and Sostdc1 signaling. In this study, we show that Sostdc1, a secreted inhibitor of the Wnt pathway, is a downstream target of Shh and hypothesize that the interaction of Wnt, Shh and Sostdc1 is a pivotal mechanism controlling the spatial patterning of palatal rugae. |
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