Meeting report: a hard look at the state of enamel research

Abstract

The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines (ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research (NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3D cell culture/organoids. Scientists from a number of disciplines, representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field.

Keywords

enamel / mineralized tissue / mineralization / ameloblast / stem cell

References

[1] Braasch I, Gehrke AR, Smith JJ. The spotted gar genome illuminates vertebrate evolution and facilitates human-teleost comparisons. Nat Genet, 2016, 48(4): 427-437.

[2] Qu Q, Haitina T, Zhu M. New genomic and fossil data illuminate the origin of enamel. Nature, 2015, 526(7571): 108-111.

[3] Sire JY. Light and TEM study of nonregenerated and experimentally regenerated scales of Lepisosteus oculatus (Holostei) with particular attention to ganoine formation. Anat Rec, 1994, 240(2): 189-207.

[4] Sire JY. Ganoine formation in the scales of primitive actinopterygian fishes, lepisosteids and polypterids. Connect Tissue Res, 1995, 33(1/2/3): 213-222.

[5] Satchell PG, Shuler CF, Diekwisch TG. True enamel covering in teeth of the Australian lungfish Neoceratodus forsteri. Cell Tissue Res, 2000, 299(1): 27-37.

[6] Ronnholm E. The amelogenesis of human teeth as revealed by electron mircoscopy I. The fine structure of the ameloblasts. J Ultrastruct Res, 1962, 6: 229-248.

[7] Smith CE, Hu Y, Hu JC. Ultrastructure of early amelogenesis in wild-type, Amelx-/-, and Enam-/- mice: enamel ribbon initiation on dentin mineral and ribbon orientation by ameloblasts. Mol Genet Genomic Med, 2016, 4(6): 662-683.

[8] Rajpar MH, Harley K, Laing C. Mutation of the gene encoding the enamel-specific protein, enamelin, causes autosomal-dominant amelogenesis imperfecta. Hum Mol Genet, 2001, 1(16): 1673-1677.

[9] Poulter JA, Murillo G, Brookes SJ. Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta. Hum Mol Genet, 2014, 23(20): 5317-5324.

[10] Lagerström M, Dahl N, Nakahori Y. A deletion in the amelogenin gene (AMG) causes X-linked amelogenesis imperfecta (AIH1). Genomics, 1991, 10(4): 971-975.

[11] Kim JW, Simmer JP, Hart TC. MMP-20 mutation in autosomal recessive pigmented hypomaturation amelogenesis imperfecta. J Med Genet, 2005, 42(3): 271-275.

[12] Doudna JA, Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science, 2014, 346(6213): 1258096.

[13] Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol, 2003, 4(7): 517-529.

[14] Clapham DE. Calcium signaling. Cell, 2007, 131(6): 1047-1058.

[15] Bootman MD, Lipp P, Berridge MJ. The organisation and functions of local Ca(2+) signals. J Cell Sci, 2001, 114(Pt 12): 2213-2222.

[16] Lacruz RS, Feske S. Diseases caused by mutations in ORAI1 and STIM1. Ann NY Acad Sci, 2015, 1356: 45-79.

[17] Eckstein M, Vaeth M, Fornai C. Store-operated Ca2+ entry controls ameloblast cell function and enamel development. JCI Insight, 2017, 2(6): e91166.

[18] Kuang-Hsien HuJ, Mushegyan V, Klein OD. On the cutting edge of organ renewal: Identification, regulation, and evolution of incisor stem cells. Genesis, 2014, 52(2): 79-92.

[19] Biehs B, Hu JK, Strauli NB. BMI1 represses Ink4a/Arf and Hox genes to regulate stem cells in the rodent incisor. Nat Cell Biol, 2013, 15(7): 846-852.

[20] Juuri E, Saito K, Ahtiainen L. Sox2+ stem cells contribute to all epithelial lineages of the tooth via Sfrp5+ progenitors. Dev Cell, 2012, 23(2): 317-328.

[21] Seidel K, Ahn CP, Lyons D. Hedgehog signaling regulates the generation of ameloblast progenitors in the continuously growing mouse incisor. Development, 2010, 137(22): 3753-3761.

[22] Seidel K, Marangoni P, Tang C et al. Resolving stem and progenitor cells in the adult mouse incisor through gene co-expression analysis. eLife 2017; 6 (pii: e24712).

[23] Klein OD, Lyons DB, Balooch G. An FGF signaling loop sustains the generation of differentiated progeny from stem cells in mouse incisors. Development, 2008, 135(2): 377-385.

[24] Jheon AH, Li CY, Wen T. Expression of microRNAs in the stem cell niche of the adult mouse incisor. PLoS One, 2011, 6(9): e24536.

[25] Goodwin AF, Tidyman WE, Jheon AH. Abnormal Ras signaling in Costello syndrome (CS) negatively regulates enamel formation. Hum Mol Genet, 2014, 23(3): 682-692.

[26] Jheon AH, Prochazkova M, Meng B. Inhibition of notch signaling during mouse incisor renewal leads to enamel defects. J Bone Miner Res, 2016, 31(1): 152-162.

[27] Sun Z, Yu W, Sanz Navarro M. Sox2 and Lef-1 interact with Pitx2 to regulate incisor development and stem cell renewal. Development, 2016, 143(22): 4115-4126.

[28] Naveau A, Zhang B, Meng B et al. Isl1 controls patterning and mineralization of enamel in the continuously renewing mouse incisor. J Bone Miner Res 2017; epub ahead of print 26 June 2017; doi: 10.1002/jbmr.3202.

[29] Zheng X, Goodwin AF, Tian H et al. Ras signaling regulates stem cells and amelogenesis in the mouse incisor. J Dent Res 2017; epub ahead of print 23 June 2017; doi: 10.1177/0022034517717255.

[30] Tapaltsyan V, Charles C, Hu J. Identification of novel Fgf enhancers and their role in dental evolution. Evol Dev, 2016, 18(1): 31-40.

[31] Tapaltsyan V, Eronen JT, Lawing AM. Continuously growing rodent molars result from a predictable quantitative evolutionary change over 50 million years. Cell reports, 2015, 11(5): 673-680.

[32] Daculsi G, Kerebel B. High-resolution electron microscope study of human enamel crystallites: size, shape, and growth. J UltrastructRes, 1978, 65(2): 163-172.

[33] Seow WK. Developmental defects of enamel and dentine: challenges for basic science research and clinical management. Aust Dent J, 2014, 59(Suppl 1): 143-154.

[34] Guatelli-Steinberg D. Analysis and significance of linear enamel hypoplasia in Plio-Pleistocene hominins. Am J Phys Anthropol, 2004, 123(3): 199-215.

[35] Ungar PS, Sponheimer M. The diets of early hominins. Science, 2011, 334(6053): 190-193.

[36] Sharma R, Tsuchiya M, Skobe Z. The acid test of fluoride: how pH modulates toxicity. PLoS One, 2010, 5(5): e10895.

[37] DenBesten PK. Biological mechanisms of dental fluorosis relevant to the use of fluoride supplements. Community DentOral Epidemiol, 1999, 27(1): 41-47.

[38] Lacruz RS, Habelitz S, Wright JT. Dental enamel formation and implications for oral health and disease. Physiol Rev, 2017, 97(3): 939-993.

[39] Wright JT, Carrion IA, Morris C. The molecular basis of hereditary enamel defects in humans. J Dent Res, 2015, 94(1): 52-61.

[40] Hu S, Parker J, Wright JT. Towards unraveling the human tooth transcriptome: the dentome. PLoS One, 2015, 10(4): e0124801.

[41] Liu H, Yan X, Pandya M et al. Daughters of the enamel organ: development, fate, and function of the stratum intermedium, stellate reticulum, and outer enamel epithelium. Stem Cells Dev 2016; epub ahead of print 9 September 2016.

[42] Andl T, Reddy ST, Gaddapara T. WNT signals are required for the initiation of hair follicle development. Dev Cell, 2002, 2(5): 643-653.

[43] Chu EY, Hens J, Andl T. Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development, 2004, 131(19): 4819-4829.

[44] Liu F, Thirumangalathu S, Gallant NM. Wnt-beta-catenin signaling initiates taste papilla development. Nat Genet, 2007, 39(1): 106-112.

[45] Liu F, Chu EY, Watt B. Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Dev Biol, 2008, 313(1): 210-224.

[46] Liu F, Dangaria S, Andl T. beta-Catenin initiates tooth neogenesis in adult rodent incisors. J Dent Res, 2010, 89(9): 909-914.

[47] Zhang Y, Andl T, Yang SH. Activation of beta-catenin signaling programs embryonic epidermis to hair follicle fate. Development, 2008, 135(12): 2161-2172.

[48] Choi YS, Zhang Y, Xu M. Distinct functions for Wnt/beta-catenin in hair follicle stem cell proliferation and survival and interfollicular epidermal homeostasis. Cell Stem Cell, 2013, 13(6): 720-733.

[49] Xu M, Horrell J, Snitow M. WNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation. Nat Commun, 2017, 8: 15397.

[50] Kollar EJ, Mina M. Role of the early epithelium in the patterning of the teeth and Meckel's cartilage. J Craniofac Genet Dev Biol, 1991, 11(4): 223-228.

[51] Thomas HF, Kollar EJ. Differentiation of odontoblasts in grafted recombinants of murine epithelial root sheath and dental mesenchyme. Arch Oral Biol, 1989, 34(1): 27-35.

[52] Mina M, Kollar EJ. The induction of odontogenesis in non-dental mesenchyme combined with early murine mandibular arch epithelium. Arch Oral Biol, 1987, 32(2): 123-127.

[53] Yoshikawa DK, Kollar EJ. Recombination experiments on the odontogenic roles of mouse dental papilla and dental sac tissues in ocular grafts. Arch Oral Biol, 1981, 26(4): 303-307.

[54] DenBesten PK, Gao C, Li W. Development and characterization of an SV40 immortalized porcine ameloblast-like cell line. Eur J Oral Sci, 1999, 107(4): 276-281.

[55] DenBesten PK, Machule D, Zhang Y. Characterization of human primary enamel organ epithelial cells in vitro. Arch Oral Biol, 2005, 50(8): 689-694.

[56] Li W, Machule D, Gao C. Growth of ameloblast-lineage cells in a three-dimensional Matrigel environment. Eur J Oral Sci, 2006, 114(Suppl 1): 159-163.

[57] Zheng LW, Linthicum L, DenBesten PK. The similarity between human embryonic stem cell-derived epithelial cells and ameloblast-lineage cells. Int J Oral Sci, 2013, 5(1): 1-6.

[58] Zheng L, Warotayanont R, Stahl J. Inductive ability of human developing and differentiated dental mesenchyme. Cells Tissues Organs, 2013, 198(2): 99-110.

[59] Free RD, DeRocher KA, Stock S. Characterization of enamel caries Lesions in rat molars using synchrotron X-ray microtomography. J Synchrotron Res, 2017, 24: 1056-1064.

[60] Gordon LM, Cohen MJ, MacRenaris KW. Amorphous intergranular phases control the properties of rodent tooth enamel. Science, 2015, 347(6223): 746-750.

[61] Fontaine AL, Zavgorodniy A, Liu H. Atomic-scale compositional mapping reveals Mg-rich amorphous calcium phospahte in human dental enamel. Sci Adv, 2016, 2(9): e1601145.

[62] Gordon LM, Joester D. Mapping residual organics and carbonate at grain boundaries and in the amorphous interphase in mouse incisor enamel. Front Physiology, 2015, 6: 57.

[63] Mann S . The biomimetics of enamel: a paradigm for organized biomaterials synthesis. Ciba Found Symp 1997205 261–274.

[64] Ruan Q, Moradian-Oldak J. Amelogenin and enamel biomimetics. J Mater Chem B, 2015, 3(16): 3112-3129.

[65] Moradian-Oldak J. The regeneration of tooth enamel. Dimens Dent Hyg, 2009, 7(8): 12-15.

[66] Moradian-Oldak J. Protein-mediated enamel mineralization. Front Biosci Landmark, 2012, 17: 1996-2023.

[67] Smith C. Cellular and chemical events during enamel maturation. Crit Rev Oral Biol Med, 1998, 9: 128-161.

[68] Ruan QC, Zhang YZ, Yang XD. An amelogenin-chitosan matrix promotes assembly of an enamel-like layer with a dense interface. Acta Biomater, 2013, 9(7): 7289-7297.

[69] Gibson CW, Yuan Z-A, Hall B. Amelogenin-deficient mice display an amelogenesis imperfecta phenotype. J Biol Chem, 2001, 276(34): 31871-31875.

[70] Aoba T, Moreno EC, Kresak M. Possible roles of partial sequences at N- and C-termini of amelogenin in protein-enamel mineral interaction. J Dent Res, 1989, 68: 1331-1336.

[71] Gungormus M, Fong H, Kim IW. Regulation of in vitro calcium phosphate mineralization by combinatorially selected hydroxyapatite-binding peptides. Biomacromolecules, 2008, 9: 966-973.

[72] Le Norcy E, Kwak SY, Wiedemann-Bidlack FB. Potential role of the amelogenin N-terminus in the regulation of calcium phosphate formation in vitro. Cells Tissues Organs, 2011, 194(2/3/4): 188-193.

[73] Margolis H, Gibson C, Diekwisch M-O. Highlights and remaining questions. Eur J Oral Sci, 2006, 114: 379-383.

[74] Moradian-Oldak J, Bouropoulos N, Wang L. Analysis of self-assembly and apatite binding properties of amelogenin proteins lacking the hydrophilic C-terminal. Matrix Biol, 2002, 21: 197-205.

[75] Moradian-Oldak J, Tan J, Fincham AG. Interaction of amelogenin with hydroxyapatite crystals: an adherence effect through amelogenin molecular self-association. Biopolymers, 1998, 46(4): 225-238.

[76] Shaw WJ, Campbell AA, Paine ML. The COOH terminus of the amelogenin, LRAP, is oriented next to the hydroxyapatite surface. J Biol Chem, 2004, 279(39): 40263-40266.

[77] Zhu L, Tanimoto K, Le T. Functional roles of prolines at amelogenin C-terminal during tooth enamel formation. Cells Tissues Organs, 2009, 189: 203-206.

[78] Tao J, Buchko GW, Shaw WJ. equence-Defined, Energetic Shifts Control the Disassembly Kinetics and Microstructure of Amelogenin Adsorbed onto Hydroxyapatite (100). Langmuir, 2015, 31: 10451-10460.

[79] Lu J, Xu YS, Buchko GW. Mineral association changes the secondary structure and dynamics of murine amelogenin. J Dent Res, 2013, 92: 1000-1004.

[80] Lu J-X, Burton SD, Xu YS. The flexible structure of the K24S28 region of leucine-rich amelogenin peptide (LRAP) bound to apatites as a function of surface type, calcium, mutation, and ionic strength. Front Physiol, 2014, 5: 1-8.

[81] Lu J-X, Qiang W, Yau W-M. Molecular structure of b-amyloid fibrils in alzheimer's disease brain tissue. Cell, 2013, 154: 1257-1268.

[82] Lu J-x, Xu YS, Shaw WJ. Phosphorylation and ionic strength alter the LRAP-HAP interface in the N-terminus. Biochemistry, 2013, 52: 21996-22205.

[83] Masica DL, Gray JJ, Shaw WJ. Partial High-Resolution Structure of Phosphorylated and Non-phosphorylated Leucine-Rich Amelogenin Protein Adsorbed to Hydroxyapatite. J Phys Chem, 2011, 115: 13775-13785.

[84] Shaw WJ, Ferris K. Structure, orientation, and dynamics of the C-terminal hexapeptide of LRAP determined using solid-state NMR. J Phys Chem B, 2008, 112(51): 16975-16981.

[85] Shaw WJ, Ferris K, Tarasevich B. The structure and orientation of the C-terminus of LRAP. Biophys J, 2008, 94(8): 3247-3257.

[86] Cho A, Haruyama N, Hall B. TGF-ss regulates enamel mineralization and maturation through KLK4 expression. PLoS One, 2013, 8(11): e82267.

[87] Hoshi K, Amizuka N, Oda K. Immunolocalization of tissue non-specific alkaline phosphatase in mice. Histochem Cell Biol, 1997, 107(3): 183-191.