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Sostdc1 Plays an Essential Role in Mammalian Tooth Patterning: Tooth Sostdc1 Plays an Essential Role in Mammalian Recent Publications in this Series: InsightintotheRodent DentalEvolution Patterning: Tooth anEssentialRoleinMammalian MUNNESostdc1Plays PAULIINA 9/2010 Manu Eeva Plant Secondary Metabolites in Peucedanum palustre and Angelica archangelica and Their Plant Cell Cultures 10/2010 Niina Kivikero Granulation in Miniaturised Fluid Bed Using Electrostatic Atomisation 11/2010 Tiina Heikkilä Miniaturization of Drug Solubility and Dissolution Testings 12/2010 Markus Haapala Heated Nebulizer Microchips for Mass Spectrometry 13/2010 Anu Hynninen Zinc, Cadmium and Lead Resistance Mechanisms in Bacteria and Their Contribution to Biosensing 14/2010 Mart Krupovič Evolutionary Genomics of Prokaryotic Viruses 15/2010 Virginija Cvirkaitė-Krupovič Entry of The Membrane-Containing Bacteriophages into Their Hosts 16/2010 Hanan T. 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Helsinki 2010 Supervised by: Professor Jukka Jernvall University of Helsinki, Finland and Professor Irma Thesleff University of Helsinki, Finland Reviewed by: Johanna Pispa, Ph.D University of Helsinki, Finland and Professor Seppo Vainio University of Oulu, Finland Opponent: Ophir Klein, M.D., Ph.D University of California, USA Custodian: Professor Juha Voipio University of Helsinki, Finland ISBN: 978-952-10-6390-9 (paperback) ISBN: 978-952-10-6391-6 (PDF) ISSN: 1795-7079 Press: Yliopistopaino, Helsinki 2010 CONTENTS LIST OF ORIGINAL PUBLICATIONS ABBREVIATIONS SUMMARY 1. INTRODUCTION ......................................................................................................... 1 2. REVIEW ON THE LITERATURE ............................................................................... 2 2.1. Neural crest ........................................................................................................... 2 2.2. Placodes and initiation of ectodermal organogenesis ........................................... 2 2.3. Tooth development ............................................................................................... 3 2.4. Enamel knot and tooth morphogenesis ................................................................. 5 2.5. Morphogens and pattern formation ...................................................................... 6 2.6. Signaling pathways in tooth development ............................................................ 7 2.6.1. Fibroblast growth factor (FGF) ................................................................. 7 2.6.2. Sonic hedgehog (Shh) ................................................................................ 8 2.6.3. Ectodysplasin (EDA) ................................................................................. 9 2.6.4. Transforming growth factor- (TGF-superfamily .............................. 9 2.6.4.1. ActivinA .................................................................................... 10 2.6.4.2. Bone morphogenetic protein (BMP) .......................................... 10 2.6.5. Wnt .......................................................................................................... 12 2.6.6. Follistatin ................................................................................................. 14 2.6.7. Sostdc1 ..................................................................................................... 14 2.7. Crosstalk between Wnt and BMP signaling ....................................................... 15 2.8. The role of TGF- family in morphoregulation ................................................. 16 2.9. Craniofacial development ................................................................................... 17 2.10. Trends in the evolution of dentition .................................................................... 19 2.11. Mouse dentition .................................................................................................. 20 2.12. Supernumerary teeth in rodents .......................................................................... 22 2.13. Dollo’s law and the timing of development ........................................................ 24 3. AIMS OF THE STUDY .............................................................................................. 25 4. MATERIALS AND METHODS ................................................................................. 26 4.1. Mouse strains ...................................................................................................... 26 4.2. Probes ................................................................................................................. 26 4.3. Methods used in articles ..................................................................................... 26 5. RESULTS AND DISCUSSION .................................................................................. 27 5.1. The role of Sostdc1 in the molar cusp delineation (I) ........................................ 27 5.2. The suppression of vestigial incisors by Sostdc1 (II, III) ................................... 29 5.3. Fine-tuning of BMP and ActivinA signaling regulates the size and number of incisors (III and unpublished results) ............................ 33 6. CONCLUDING REMARKS ....................................................................................... 39 ACKNOWLEDGEMENTS ............................................................................................. 42 REFERENCES ................................................................................................................ 44 LIST OF ORIGINAL PUBLICATIONS This thesis is based on the following original articles (referred in the text by their Roman numerals) and some unpublished results. I Kassai, Y.*, Munne, P.*, Hotta, Y., Penttilä, E., Kavanagh, K., Ohbayashi, N., Takada, S.,Thesleff, I., Jernvall, J., Itoh, N. (2005). Regulation of mammalian tooth cusp patterning by ectodin. Science 309, 2067-2070. * These authors contributed equally to this work II Munne, P.M., Tummers, M., Järvinen, E., Thesleff, I., Jernvall, J. (2009). Tinkering with the inductive mesenchyme: Sostdc1/Ectodin uncovers the role of dental mesenchyme in limiting tooth induction. Development 136 (3), 393-402. III Munne, P.M., Felszeghy, S., Jussila, M., Suomalainen, M., Thesleff, I., Jernvall, J. (2010). Splitting placodes: effects of bone morphogenetic protein and Activin on the patterning and identity of mouse incisors. Evolution & Development 12, 383-392. The articles are printed with kind permission of their copyright holders. ABBREVIATIONS AER apical ectodermal ridge APC Adenomatous polyposis coli BMP Bone morphogenetic protein BMPR Bone morphogenetic protein receptor BrdU Bromodeoxyuridine, synthetic nucleoside. Incorporates in proliferating cells. BSA bovine serum albumin CaM1 Calmodulin1
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