Histochemistry and Cell Biology

, Volume 136, Issue 6, pp 663–675 | Cite as

Shh signaling is essential for rugae morphogenesis in mice

  • 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 JungEmail author
Original Paper


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.


Rugae patterning Wnt Shh Sostdc1 Reaction–diffusion 



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).

Supplementary material

418_2011_870_MOESM1_ESM.tif (6 mb)
Supplementary figure 1. Gli1, Bmp4 and Lrp4 expression patterns in rugae following 5E1 injection. (a, a′, d, d′) Gli1 expression is reduced in the palatal ridge 24 h after 5E1 delivery. (b, b′, e, e′, c, c′, f, f′) Bmp4 and Lrp4 expression are not altered 24 h after 5E1 injection. (g, g′, j, j′) Gli1 expression is clearly reduced in the palatal ridge 48 h after 5E1 injection. (i, i′, l, l′) Lrp4 expression is not altered 48 h after 5E1 injection. (h, h′, k, k′) In the control group, Bmp4 is expressed along the first three rugae lane. However, Bmp4 expression was detected in only in the first rugae following 5E1 treatment. Scale bar; a-l: 500 μm, a′–l′ : 100 μm. (TIFF 6138 kb)
418_2011_870_MOESM2_ESM.tif (305 kb)
Supplementary figure 2. Alteration of Wnt/β-catenin signaling levels following 5E1 injection. Gene expression levels are examined by microarray. The Wnt/β-catenin downstream genes, Axin2, Dkk1 and Gata3, expression levels are up-regulated after 5E1 treatment. (TIFF 305 kb)

Supplementary movie 1. An additional row of cells is inserted into the anterior part of the #8 ruga. Newly formed rugae appeared following the reaction–diffusion model that consists of activator, mediator and inhibitor. The lateral extension is simulated by the addition of a new column of cells to the edge of the field between #3 and #4 rugae formations. (MP4 1272 kb)


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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Jong-Min Lee
    • 1
  • Seita Miyazawa
    • 2
  • Jeong-Oh Shin
    • 1
  • Hyuk-Jae Kwon
    • 1
  • Dae-Woon Kang
    • 3
  • Byung-Jai Choi
    • 3
  • Jae-Ho Lee
    • 3
  • Shigeru Kondo
    • 2
  • Sung-Won Cho
    • 1
  • Han-Sung Jung
    • 1
    Email author
  1. 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 BiotechnologyYonsei UniversitySeoulKorea
  2. 2.Graduate School of Frontier BiosciencesOsaka UniversityOsakaJapan
  3. 3.Department of Pediatric Dentistry, Oral Science Research CenterCollege of Dentistry, Yonsei UniversitySeoulKorea

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