The development of a tooth germ in a precise size, shape, and position in the jaw, involves meticulous regulation of cell proliferation and cell death. Apoptosis, as the most common type of programmed cell death during embryonic development, plays a number of key roles during odontogenesis, ranging from the budding of the oral epithelium during tooth initiation, to later tooth germ morphogenesis and removal of enamel knot signaling center. Here, we summarize recent knowledge about the distribution and function of apoptotic cells during odontogenesis in several vertebrate lineages, with a special focus on amniotes (mammals and reptiles). We discuss the regulatory roles that apoptosis plays on various cellular processes during odontogenesis. We also review apoptosis-associated molecular signaling during tooth development, including its relationship with the autophagic pathway. Lastly, we cover apoptotic pathway disruption, and alterations in apoptotic cell distribution in transgenic mouse models. These studies foster a deeper understanding how apoptotic cells affect cellular processes during normal odontogenesis, and how they contribute to dental disorders, which could lead to new avenues of treatment in the future.

Department of Biological Sciences SUNY Oswego Oswego NY United States

Department of Experimental Biology Faculty of Science Masaryk University Brno Czechia

Department of Natural Sciences University of Michigan Dearborn Dearborn MI United States

Laboratory of Molecular Morphogenesis Institute of Animal Physiology and Genetics Czech Academy of Sciences Brno Czechia

Zobrazit více v PubMed

Andl T., Ahn K., Kairo A., Chu E. Y., Wine-Lee L., Reddy S. T., et al. (2004). Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development. Development 131 2257–2268. PubMed

Arakawa S., Tsujioka M., Yoshida T., Tajima-Sakurai H., Nishida Y., Matsuoka Y., et al. (2017). Role of Atg5-dependent cell death in the embryonic development of Bax/Bak double-knockout mice. Cell Death. Differ. 24 1598–1608. 10.1038/cdd.2017.84 PubMed DOI PMC

Asher R. J., Meng J., Wible J. R., Mckenna M. C., Rougier G. W., Dashzeveg D., et al. (2005). Stem Lagomorpha and the antiquity of Glires. Science 307 1091–1094. 10.1126/science.1107808 PubMed DOI

Bali R., Chandra A., Verma R. (2013). Apoptosis in normal oral tissues and odontogenesis. Eur. J. Gen. Dent. 2 195–198. 10.4103/2278-9626.115974 DOI

Balic A. (2019). Concise review: cellular and molecular mechanisms regulation of tooth initiation. Stem Cells 37 26–32. 10.1002/stem.2917 PubMed DOI

Balic A., Thesleff I. (2015). Tissue interactions regulating tooth development and renewal. Curr. Top. Dev. Biol. 115 157–186. 10.1016/bs.ctdb.2015.07.006 PubMed DOI

Bei M. (2009). Molecular genetics of ameloblast cell lineage. J. Exp. Zool. Part B Mol. Dev. Evol. 312 437–444. 10.1002/jez.b.21261 PubMed DOI PMC

Bei M., Stowell S., Maas R. (2004). Msx2 controls ameloblast terminal differentiation. Dev. Dyn. 231 758–765. 10.1002/dvdy.20182 PubMed DOI

Blackburn J., Kawasaki K., Porntaveetus T., Kawasaki M., Otsuka-Tanaka Y., Miake Y., et al. (2015). Excess NF-κB induces ectopic odontogenesis in embryonic incisor epithelium. J. Dent. Res. 94 121–128. 10.1177/0022034514556707 PubMed DOI PMC

Blecher S. R. (1986). Anhidrosis and absence of sweat glands in mice hemizygous for the Tabby gene: supportive evidence for the hypothesis of homology between Tabby and human anhidrotic (hypohidrotic) ectodermal dysplasia (Christ-Siemens-Touraine syndrome). J. Invest. Dermatol. 87 720–722. 10.1111/1523-1747.ep12456718 PubMed DOI

Boatright K. M., Salvesen G. S. (2003). Mechanisms of caspase activation. Curr. Opin. Cell Biol. 15 725–731. 10.1016/j.ceb.2003.10.009 PubMed DOI

Bodur C., Kutuk O., Tezil T., Basaga H. (2012). Inactivation of Bcl-2 through IκB kinase (IKK)-dependent phosphorylation mediates apoptosis upon exposure to 4-hydroxynonenal (HNE). J. Cell. Physiol. 227 3556–3565. 10.1002/jcp.24057 PubMed DOI

Boran T., Lesot H., Peterka M., Peterkova R. (2005). Increased apoptosis during morphogenesis of the lower cheek teeth in tabby/EDA mice. J. Dent. Res. 84 228–233. 10.1177/154405910508400304 PubMed DOI

Bosshardt D. D., Selvig K. A. (1997). Dental cementum: the dynamic tissue covering of the root. Periodontol 2000 13 41–75. 10.1111/j.1600-0757.1997.tb00095.x PubMed DOI

Boya P., Kroemer G. (2009). Beclin 1: a BH3-only protein that fails to induce apoptosis. Oncogene 28 2125–2127. 10.1038/onc.2009.83 PubMed DOI

Brentnall M., Rodriguez-Menocal L., De Guevara R. L., Cepero E., Boise L. H. (2013). Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol. 14:32. 10.1186/1471-2121-14-32 PubMed DOI PMC

Bronckers A. L., Goei S. W., Dumont E., Lyaruu D. M., Wöltgens J. H., Van Heerde W. L., et al. (2000). In situ detection of apoptosis in dental and periodontal tissues of the adult mouse using annexin-V-biotin. Histochem. Cell Biol. 113 293–301. 10.1007/s004180000137 PubMed DOI

Bronckers A. L., Lyaruu D. M., Goei W., Litz M., Luo G., Karsenty G., et al. (1996). Nuclear DNA fragmentation during postnatal tooth development of mouse and hamster and during dentin repair in the rat. Eur. J. Oral Sci. 104 102–111. 10.1111/j.1600-0722.1996.tb00053.x PubMed DOI

Buchtová M., Boughner J. C., Fu K., Diewert V. M., Richman J. M. (2007). Embryonic development of Python sebae - II: craniofacial microscopic anatomy, cell proliferation and apoptosis. Zoology 110 231–251. 10.1016/j.zool.2007.01.006 PubMed DOI

Buchtová M., Handrigan G. R., Tucker A. S., Lozanoff S., Town L., Fu K., et al. (2008). Initiation and patterning of the snake dentition are dependent on Sonic hedgehog signaling. Dev. Biol. 319 132–145. 10.1016/j.ydbio.2008.03.004 PubMed DOI

Buchtová M., Stembírek J., Glocová K., Matalová E., Tucker A. S. (2012). Early regression of the dental lamina underlies the development of diphyodont dentitions. J. Dent. Res. 91 491–498. 10.1177/0022034512442896 PubMed DOI

Buchtová M., Zahradníèek O., Balková S., Tucker A. S. (2013). Odontogenesis in the veiled chameleon (Chamaeleo calyptratus). Arch. Oral. Biol. 58 118–133. 10.1016/j.archoralbio.2012.10.019 PubMed DOI

Burgoyne L. A. (1999). The mechanisms of pyknosis: hypercondensation and death. Exp. Cell Res. 248 214–222. 10.1006/excr.1999.4406 PubMed DOI

Cecconi F., Levine B. (2008). The role of autophagy in mammalian development: cell makeover rather than cell death. Dev. Cell 15 344–357. 10.1016/j.devcel.2008.08.012 PubMed DOI PMC

Cerri P. S., Freymüller E., Katchburian E. (2000). Apoptosis in the early developing periodontium of rat molars. Anat. Rec. 258 136–144. 10.1002/(sici)1097-0185(20000201)258:2<136::aid-ar3>3.0.co;2-l PubMed DOI

Cerri P. S., Katchburian E. (2005). Apoptosis in the epithelial cells of the rests of Malassez of the periodontium of rat molars. J. Periodontal Res. 40 365–372. 10.1111/j.1600-0765.2005.00810.x PubMed DOI

Chandler J. M., Cohen G. M., Macfarlane M. (1998). Different subcellular distribution of caspase-3 and caspase-7 following Fas-induced apoptosis in mouse liver. J. Biol. Chem. 273 10815–10818. 10.1074/jbc.273.18.10815 PubMed DOI

Chang H. Y., Yang X. (2000). Proteases for cell suicide: functions and regulation of caspases. Microbiol. Mol. Biol. Rev. 64 821–846. 10.1128/mmbr.64.4.821-846.2000 PubMed DOI PMC

Charles C., Hovorakova M., Ahn Y., Lyons D. B., Marangoni P., Churava S., et al. (2011). Regulation of tooth number by fine-tuning levels of receptor-tyrosine kinase signaling. Development 138 4063–4073. 10.1242/dev.069195 PubMed DOI PMC

Chaudhry A., Sobti G. (2020). Imaging characteristics of gubernacular tract on CBCT- a pictorial review. Oral Radiol. [Epub ahead of print] 10.1007/s11282-020-00461-y PubMed DOI

Chen H., Guo S., Xia Y., Yuan L., Lu M., Zhou M., et al. (2018). The role of Rho-GEF Trio in regulating tooth root development through the p38 MAPK pathway. Exp. Cell Res. 372 158–167. 10.1016/j.yexcr.2018.09.022 PubMed DOI

Chen Q., Samaranayake L. P., Zhen X., Luo G., Nie M., Li B. (1999). Up-regulation of Fas ligand and down-regulation of Fas expression in oral carcinogenesis. Oral Oncol. 35 548–553. 10.1016/s1368-8375(99)00029-9 PubMed DOI

Cho M. I., Garant P. R. (1988). Ultrastructural evidence of directed cell migration during initial cementoblast differentiation in root formation. J. Periodontal Res. 23 268–276. 10.1111/j.1600-0765.1988.tb01371.x PubMed DOI

Cho S. W., Lee H. A., Cai J., Lee M. J., Kim J. Y., Ohshima H., et al. (2007). The primary enamel knot determines the position of the first buccal cusp in developing mice molars. Differentiation 75 441–451. 10.1111/j.1432-0436.2006.00153.x PubMed DOI

Choi S. J., Song I. S., Feng J. Q., Gao T., Haruyama N., Gautam P., et al. (2010). Mutant DLX 3 disrupts odontoblast polarization and dentin formation. Dev. Biol. 344 682–692. 10.1016/j.ydbio.2010.05.499 PubMed DOI PMC

Clark G. A. (1961). Occurrence and timing of egg teeth in birds. Wilson Bull. 73 268–278.

Coin R., Kieffer S., Lesot H., Vonesch J. L., Ruch J. V. (2000). Inhibition of apoptosis in the primary enamel knot does not affect specific tooth crown morphogenesis in the mouse. Int. J. Dev. Biol. 44 389–396. PubMed

Coin R., Lesot H., Vonesch J. L., Haikel Y., Ruch J. V. (1999). Aspects of cell proliferation kinetics of the inner dental epithelium during mouse molar and incisor morphogenesis: a reappraisal of the role of the enamel knot area. Int. J. Dev. Biol. 43 261–267. PubMed

Dai J., Si J., Ouyang N., Zhang J., Wu D., Wang X., et al. (2017). Dental and periodontal phenotypes of Dlx2 overexpression in mice. Mol. Med. Rep. 15 2443–2450. 10.3892/mmr.2017.6315 PubMed DOI PMC

Davit-Beal T., Chisaka H., Delgado S., Sire J. Y. (2007). Amphibian teeth: current knowledge, unanswered questions, and some directions for future research. Biol. Rev. Camb. Philos. Soc. 82 49–81. 10.1111/j.1469-185x.2006.00003.x PubMed DOI

de Pizzol Júnior J. P., Sasso-Cerri E., Cerri P. S. (2015). Apoptosis and reduced microvascular density of the lamina propria during tooth eruption in rats. J. Anat. 227 487–496. 10.1111/joa.12359 PubMed DOI PMC

Debatin K. M., Krammer P. H. (2004). Death receptors in chemotherapy and cancer. Oncogene 23 2950–2966. 10.1038/sj.onc.1207558 PubMed DOI

Debiais-Thibaud M., Chiori R., Enault S., Oulion S., Germon I., Martinand-Mari C., et al. (2015). Tooth and scale morphogenesis in shark: an alternative process to the mammalian enamel knot system. BMC Evol. Biol. 15:292. 10.1186/s12862-015-0557-0 PubMed DOI PMC

DeMar R. (1972). Evolutionary implications of Zahnreihen. Evolution 26 435–450. 10.2307/2407018 PubMed DOI

Domon T., Osanai M., Yasuda M., Seki E., Takahashi S., Yamamoto T., et al. (1997). Mononuclear odontoclast participation in tooth resorption: the distribution of nuclei in human odontoclasts. Anat. Rec. 249 449–457. 10.1002/(sici)1097-0185(199712)249:4<449::aid-ar4>3.0.co;2-m PubMed DOI

Domon T., Taniguchi Y., Inoue K., Ushijima N., Taishi Y., Hiramatsu A., et al. (2008). Apoptosis of odontoclasts under physiological root resorption of human deciduous teeth. Cell Tissue Res. 331 423–433. 10.1007/s00441-007-0525-0 PubMed DOI

Dosedelova H., Dumková J., Lesot H., Glocová K., Kunová M., Tucker A. S., et al. (2015). Fate of the molar dental lamina in the monophyodont mouse. PLoS One 10:e0127543. 10.1371/journal.pone.0127543 PubMed DOI PMC

Edmund A. G. (1960). Tooth replacement phenomena in the lower vertebrates. R. Ont. Mus. Life Sci. 52 1–190.

Edwin F., Patel T. B. (2008). A novel role of Sprouty 2 in regulating cellular apoptosis. J. Biol. Chem. 283 3181–3190. 10.1074/jbc.m706567200 PubMed DOI PMC

Faleiro L., Lazebnik Y. (2000). Caspases disrupt the nuclear-cytoplasmic barrier. J. Cell Biol. 151 951–960. 10.1083/jcb.151.5.951 PubMed DOI PMC

Fan T. J., Han L. H., Cong R. S., Liang J. (2005). Caspase family proteases and apoptosis. Acta Biochim. Biophys. Sin. 37 719–727. 10.1111/j.1745-7270.2005.00108.x PubMed DOI

Feng J. Q., Ward L. M., Liu S., Lu Y., Xie Y., Yuan B., et al. (2006). Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat. Genet. 38 1310–1315. 10.1038/ng1905 PubMed DOI PMC

Ferguson B. M., Brockdorff N., Formstone E., Ngyuen T., Kronmiller J. E., Zonana J. (1997). Cloning of Tabby, the murine homolog of the human EDA gene: evidence for a membrane-associated protein with a short collagenous domain. Hum. Mol. Genet. 6 1589–1594. 10.1093/hmg/6.9.1589 PubMed DOI

Fernando P., Megeney L. A. (2007). Is caspase-dependent apoptosis only cell differentiation taken to the extreme? FASEB J. 21 8–17. 10.1096/fj.06-5912hyp PubMed DOI

Fischer U., Jänicke R. U., Schulze-Osthoff K. (2003). Many cuts to ruin: a comprehensive update of caspase substrates. Cell Death Differ. 10 76–100. 10.1038/sj.cdd.4401160 PubMed DOI PMC

Flor A. C., Wolfgeher D., Wu D., Kron S. J. (2017). A signature of enhanced lipid metabolism, lipid peroxidation and aldehyde stress in therapy-induced senescence. Cell Death Discov. 3:17075. PubMed PMC

Foghi A., Teerds K. J., Van Der Donk H., Moore N. C., Dorrington J. (1998). Induction of apoptosis in thecal/interstitial cells: action of transforming growth factor (TGF) alpha plus TGF beta on bcl-2 and interleukin-1 beta-converting enzyme. J. Endocrinol. 157 489–494. PubMed

Fons J. M., Gaete M., Zahradnicek O., Landova M., Bandali H., Khannoon E. R., et al. (2020). Getting out of an egg: merging of tooth germs to create an egg tooth in the snake. Dev. Dyn. 249 199–208. 10.1002/dvdy.120 PubMed DOI

Francis J. M., Heyworth C. M., Spooncer E., Pierce A., Dexter T. M., Whetton A. D. (2000). Transforming growth factor-beta 1 induces apoptosis independently of p53 and selectively reduces expression of Bcl-2 in multipotent hematopoietic cells. J. Biol. Chem. 275 39137–39145. 10.1074/jbc.m007212200 PubMed DOI

Franquin J. C., Remusat M., Abou Hashieh I., Dejou J. (1998). Immunocytochemical detection of apoptosis in human odontoblasts. Eur. J. Oral Sci. 106(Suppl. 1), 384–387. 10.1111/j.1600-0722.1998.tb02202.x PubMed DOI

Fu T. M., Li Y., Lu A., Li Z., Vajjhala P. R., Cruz A. C., et al. (2016). Cryo-EM structure of Caspase-8 tandem DED filament reveals assembly and regulation mechanisms of the death-inducing signaling complex. Mol. Cell 64 236–250. 10.1016/j.molcel.2016.09.009 PubMed DOI PMC

Garcia M. A., Nelson W. J., Chavez N. (2018). Cell-cell junctions organize structural and signaling networks. Cold Spring Harb. Perspect. Biol. 10:a029181. 10.1101/cshperspect.a029181 PubMed DOI PMC

Gavrieli Y., Sherman Y., Ben-Sasson S. A. (1992). Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J. Cell Biol. 119 493–501. 10.1083/jcb.119.3.493 PubMed DOI PMC

Ghose P., Shaham S. (2020). Cell death in animal development. Development 147:dev191882. PubMed PMC

Gillette R. (1955). The dynamics of continuous succession of teeth in the frog (Rana pipiens). Am. J. Anat. 96 1–36. 10.1002/aja.1000960102 PubMed DOI

Gillis J. A., Donoghue P. C. (2007). The homology and phylogeny of chondrichthyan tooth enameloid. J. Morphol. 268 33–49. 10.1002/jmor.10501 PubMed DOI

Gonçalves J. S., Sasso-Cerri E., Cerri P. S. (2008). Cell death and quantitative reduction of rests of Malassez according to age. J. Periodontal Res. 43 478–481. 10.1111/j.1600-0765.2007.01050.x PubMed DOI

Greenham L. W., Greenham V. (1977). Sexing mouse pups. Lab. Anim. 11 181–184. 10.1258/002367777780936620 PubMed DOI

Grüneberg H. (1971). The glandular aspects of the tabby syndrome in the mouse. J. Embryol. Exp. Morphol. 25 1–19. 10.1242/dev.25.1.1 PubMed DOI

Guo H., Zhang L., Wei K., Zhao J., Wang Y., Jin F., et al. (2015). Exposure to a continuous low dose of tetrachlorodibenzo-p-dioxin impairs the development of the tooth root in lactational rats and alters the function of apical papilla-derived stem cells. Arch. Oral Biol. 60 199–207. 10.1016/j.archoralbio.2014.10.001 PubMed DOI

Hakem R., Hakem A., Duncan G. S., Henderson J. T., Woo M., Soengas M. S., et al. (1998). Differential requirement for caspase 9 in apoptotic pathways in vivo. Cell 94 339–352. 10.1016/s0092-8674(00)81477-4 PubMed DOI

Hamamoto Y., Nakajima T., Ozawa H. (1989). Ultrastructural and histochemical study on the morphogenesis of epithelial rests of Malassez. Arch. Histol. Cytol. 52 61–70. 10.1679/aohc.52.61 PubMed DOI

Han J., Ito Y., Yeo J. Y., Sucov H. M., Maas R., Chai Y. (2003). Cranial neural crest-derived mesenchymal proliferation is regulated by msx1-mediated p19ink4d expression during odontogenesis. Dev. Biol. 261 183–196. 10.1016/s0012-1606(03)00300-2 PubMed DOI

Handrigan G. R., Richman J. M. (2010). Autocrine and paracrine Shh signaling are necessary for tooth morphogenesis, but not tooth replacement in snakes and lizards (Squamata). Dev. Biol. 337 171–186. 10.1016/j.ydbio.2009.10.020 PubMed DOI

Handrigan G. R., Richman J. M. (2011). Unicuspid and bicuspid tooth crown formation in squamates. J. Exp. Zool. B Mol. Dev. Evol. 316 598–608. 10.1002/jez.b.21438 PubMed DOI

Hasegawa N., Kawaguchi H., Ogawa T., Uchida T., Kurihara H. (2003). Immunohistochemical characteristics of epithelial cell rests of Malassez during cementum repair. J. Periodontal Res. 38 51–56. 10.1034/j.1600-0765.2003.01636.x PubMed DOI

Hatakeyama S., Tomichi N., Ohara-Nemoto Y., Satoh M. (2000). The immunohistochemical localization of Fas and Fas ligand in jaw bone and tooth germ of human fetuses. Calcif. Tissue Int. 66 330–337. 10.1007/s002230010069 PubMed DOI

He J., Jing J., Feng J., Han X., Yuan Y., Guo T., et al. (2021). Lhx6 regulates canonical Wnt signaling to control the fate of mesenchymal progenitor cells during mouse molar root patterning. PLoS Genet. 17:e1009320. 10.1371/journal.pgen.1009320 PubMed DOI PMC

Hermyt M., Janiszewska K., Rupik W. (2020). Squamate egg tooth development revisited using three-dimensional reconstructions of brown anole (Anolis sagrei, Squamata, Dactyloidae) dentition. J. Anat. 236 1004–1020. 10.1111/joa.13166 PubMed DOI PMC

Hermyt M., Kaczmarek P., Kowalska M., Rupik W. (2017). Development of the egg tooth–The tool facilitating hatching of squamates: lessons from the grass snake Natrix natrix. Zool. Anzeiger 266 61–70. 10.1016/j.jcz.2016.11.001 DOI

Hosoya A., Kim J. Y., Cho S. W., Jung H. S. (2008). BMP4 signaling regulates formation of Hertwig’s epithelial root sheath during tooth root development. Cell Tissue Res. 333 503–509. 10.1007/s00441-008-0655-z PubMed DOI

Hu J. C., Lertlam R., Richardson A. S., Smith C. E., Mckee M. D., Simmer J. P. (2011). Cell proliferation and apoptosis in enamelin null mice. Eur. J. Oral Sci. 119(Suppl. 1), 329–337. 10.1111/j.1600-0722.2011.00860.x PubMed DOI PMC

Hughes M. A., Powley I. R., Jukes-Jones R., Horn S., Feoktistova M., Fairall L., et al. (2016). Co-operative and hierarchical binding of c-FLIP and Caspase-8: a unified model defines how c-FLIP isoforms differentially control cell fate. Mol. Cell 61 834–849. 10.1016/j.molcel.2016.02.023 PubMed DOI PMC

Huysseune A., Sire J. Y. (1998). Evolution of patterns and processes in teeth and tooth-related tissues in non-mammalian vertebrates. Eur. J. Oral Sci. 106(Suppl. 1), 437–481. 10.1111/j.1600-0722.1998.tb02211.x PubMed DOI

Irie K., Ozawa H. (1990). Relationships between tooth eruption, occlusion and alveolar bone resorption: histochemical and cytological studies of bone remodeling on rat incisor alveolar bone facing the enamel after root resection. Arch. Histol. Cytol. 53 511–522. 10.1679/aohc.53.511 PubMed DOI

Järvinen E., Välimäki K., Pummila M., Thesleff I., Jernvall J. (2008). The taming of the shrew milk teeth. Evol. Dev. 10 477–486. 10.1111/j.1525-142x.2008.00258.x PubMed DOI

Jernvall J., Aberg T., Kettunen P., Keränen S., Thesleff I. (1998). The life history of an embryonic signaling center: BMP-4 induces p21 and is associated with apoptosis in the mouse tooth enamel knot. Development 125 161–169. 10.1242/dev.125.2.161 PubMed DOI

Jernvall J., Keränen S. V., Thesleff I. (2000). Evolutionary modification of development in mammalian teeth: quantifying gene expression patterns and topography. Proc. Natl. Acad. Sci. U.S.A. 97 14444–14448. 10.1073/pnas.97.26.14444 PubMed DOI PMC

Jernvall J., Kettunen P., Karavanova I., Martin L. B., Thesleff I. (1994). Evidence for the role of the enamel knot as a control center in mammalian tooth cusp formation: non-dividing cells express growth stimulating Fgf-4 gene. Int. J. Dev. Biol. 38 463–469. PubMed

Jernvall J., Thesleff I. (2000). Reiterative signaling and patterning during mammalian tooth morphogenesis. Mech. Dev. 92 19–29. 10.1016/s0925-4773(99)00322-6 PubMed DOI

Josephsen K., Fejerskov O., Baelum V., Weile V. (1990). The effect of a single dose of 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) on presecretory ameloblast differentiation in rat incisors. J. Biol. Buccale 18 321–337. PubMed

Kabeya Y., Mizushima N., Ueno T., Yamamoto A., Kirisako T., Noda T., et al. (2000). LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J. 19 5720–5728. 10.1093/emboj/19.21.5720 PubMed DOI PMC

Kaliboviæ Govorko D., Beèiæ T., Vukojeviæ K., Mardešiæ-Brakus S., Bioèina-Lukenda D., Saraga-Babiæ M. (2010). Spatial and temporal distribution of Ki-67 proliferation marker, Bcl-2 and Bax proteins in the developing human tooth. Arch. Oral Biol. 55 1007–1016. 10.1016/j.archoralbio.2010.07.024 PubMed DOI

Kallenbach E. (1974). Fine structure of rat incisor ameloblasts in transition between enamel secretion and maturation stages. Tissue Cell 6 173–190. 10.1016/0040-8166(74)90030-5 PubMed DOI

Kamada S., Kikkawa U., Tsujimoto Y., Hunter T. (2005). Nuclear translocation of caspase-3 is dependent on its proteolytic activation and recognition of a substrate-like protein (s). J. Biol. Chem. 280 857–860. 10.1074/jbc.c400538200 PubMed DOI

Kaneko H., Hashimoto S., Enokiya Y., Ogiuchi H., Shimono M. (1999). Cell proliferation and death of Hertwig’s epithelial root sheath in the rat. Cell Tissue Res. 298 95–103. 10.1007/s004419900061 PubMed DOI

Kaneko H., Ogiuchi H., Shimono M. (1997). Cell death during tooth eruption in the rat: surrounding tissues of the crown. Anat. Embryol. 195 427–434. 10.1007/s004290050062 PubMed DOI

Karcher-Djuricic V., Staubli A., Meyer J. M., Ruch J. V. (1985). Acellular dental matrices promote functional differentiation of ameloblasts. Differentiation 29 169–175. 10.1111/j.1432-0436.1985.tb00311.x PubMed DOI

Kassai Y., Munne P., Hotta Y., Penttilä E., Kavanagh K., Ohbayashi N., et al. (2005). Regulation of mammalian tooth cusp patterning by ectodin. Science 309 2067–2070. 10.1126/science.1116848 PubMed DOI

Kaung H. C. (1975). Development of beaks of Rana pipiens larvae. Anat. Rec. 182 401–413. 10.1002/ar.1091820402 PubMed DOI

Kawashima N., Okiji T. (2016). Odontoblasts: specialized hard-tissue-forming cells in the dentin-pulp complex. Cong. Anom. 56 144–153. 10.1111/cga.12169 PubMed DOI

Keränen S. V. E., Åberg T., Kettunen P., Thesleff I., Jernvall J. (1998). Association of developmental regulatory genes with the development of different molar tooth shapes in two species of rodents. Dev. Genes Evol. 208 477–486. 10.1007/s004270050206 PubMed DOI

Kettunen P., Thesleff I. (1998). Expression and function of FGFs-4, -8, and -9 suggest functional redundancy and repetitive use as epithelial signals during tooth morphogenesis. Dev. Dyn. 211 256–268. 10.1002/(sici)1097-0177(199803)211:3<256::aid-aja7>3.0.co;2-g PubMed DOI

Khaejornbut J., Wilson D. J., Owens P. D. (1991). The development and fate of the dental lamina of the mandibular first molar tooth in the rat. J. Anat. 179 85–96. PubMed PMC

Kieffer S., Peterkova R., Vonesch J. L., Ruch J. V., Peterka M., Lesot H. (1999). Morphogenesis of the lower incisor in the mouse from the bud to early bell stage. Int. J. Dev. Biol. 43 531–539. PubMed

Kieser J. A., Klapsidis C., Law L., Marion M. (1993). Heterodonty and patterns of tooth replacement in Crocodylus niloticus. J. Morphol. 218 195–201. 10.1002/jmor.1052180208 PubMed DOI

Kindaichi K. (1980). An electron microscopic study of cell death in molar tooth germ epithelia of mouse embryos. Arch. Histol. Japonicum 43 289–304. 10.1679/aohc1950.43.289 PubMed DOI

Kitamura C., Kimura K., Nakayama T., Toyoshima K., Terashita M. (2001). Primary and secondary induction of apoptosis in odontoblasts after cavity preparation of rat molars. J. Dent. Res. 80 1530–1534. 10.1177/00220345010800061001 PubMed DOI

Klein O. D., Minowada G., Peterkova R., Kangas A., Yu B. D., Lesot H., et al. (2006). Sprouty genes control diastema tooth development via bidirectional antagonism of epithelial-mesenchymal FGF signaling. Dev. Cell 11 181–190. 10.1016/j.devcel.2006.05.014 PubMed DOI PMC

Klionsky D. J., Emr S. D. (2000). Autophagy as a regulated pathway of cellular degradation. Science 290 1717–1721. 10.1126/science.290.5497.1717 PubMed DOI PMC

Kondo S., Tamura Y., Bawden J. W., Tanase S. (2001). The immunohistochemical localization of Bax and Bcl-2 and their relation to apoptosis during amelogenesis in developing rat molars. Arch. Oral Biol. 46 557–568. 10.1016/s0003-9969(00)00139-4 PubMed DOI

Krajewski S., Hugger A., Krajewska M., Reed J. C., Mai J. K. (1998). Developmental expression patterns of Bcl-2, Bcl-x, Bax, and Bak in teeth. Cell Death Differ. 5 408–415. 10.1038/sj.cdd.4400360 PubMed DOI

Kratochwil K., Galceran J., Tontsch S., Roth W., Grosschedl R. (2002). FGF4, a direct target of LEF1 and Wnt signaling, can rescue the arrest of tooth organogenesis in Lef1(-/-) mice. Genes Dev. 16 3173–3185. 10.1101/gad.1035602 PubMed DOI PMC

Kuida K., Haydar T. F., Kuan C. Y., Gu Y., Taya C., Karasuyama H., et al. (1998). Reduced apoptosis and cytochrome c–mediated caspase activation in mice lacking caspase 9. Cell 94 325–337. 10.1016/s0092-8674(00)81476-2 PubMed DOI

Kumakami-Sakano M., Otsu K., Fujiwara N., Harada H. (2014). Regulatory mechanisms of Hertwig×s epithelial root sheath formation and anomaly correlated with root length. Exp. Cell Res. 325 78–82. 10.1016/j.yexcr.2014.02.005 PubMed DOI

Kumamoto H., Kimi K., Ooya K. (2001). Immunohistochemical analysis of apoptosis-related factors (Fas, Fas ligand, caspase-3 and single-stranded DNA) in ameloblastomas. J. Oral Pathol. Med. 30 596–602. 10.1034/j.1600-0714.2001.301004.x PubMed DOI

Kwon H. K., Lee J. H., Shin H. J., Kim J. H., Choi S. (2015). Structural and functional analysis of cell adhesion and nuclear envelope nano-topography in cell death. Sci. Rep. 5:15623. PubMed PMC

Lacruz R. S., Habelitz S., Wright J. T., Paine M. L. (2017). Dental enamel formation and implications for oral health and disease. Physiol. Rev. 97 939–993. 10.1152/physrev.00030.2016 PubMed DOI PMC

Lagronova-Churava S., Spoutil F., Vojtechova S., Lesot H., Peterka M., Klein O. D., et al. (2013). The dynamics of supernumerary tooth development are differentially regulated by Sprouty genes. J. Exp. Zool. B Mol. Dev. Evol. 320 307–320. 10.1002/jez.b.22502 PubMed DOI

Landova Sulcova M., Zahradnicek O., Dumkova J., Dosedelova H., Krivanek J., Hampl M., et al. (2020). Developmental mechanisms driving complex tooth shape in reptiles. Dev. Dyn. 249 441–464. 10.1002/dvdy.138 PubMed DOI

Lavrik I., Golks A., Krammer P. H. (2005). Death receptor signaling. J. Cell Sci. 118 265–267. PubMed

LeBlanc A. R. H., Paparella I., Lamoureux D. O., Doschak M. R., Caldwell M. W. (2021). Tooth attachment and pleurodont implantation in lizards: histology, development, and evolution. J. Anat. 238 1156–1178. PubMed PMC

Lee D. S., Park J. T., Kim H. M., Ko J. S., Son H. H., Gronostajski R. M., et al. (2009). Nuclear factor IC is essential for odontogenic cell proliferation and odontoblast differentiation during tooth root development. J. Biol. Chem. 284 17293–17303. 10.1074/jbc.m109.009084 PubMed DOI PMC

Lee J. H., Lee D. S., Nam H., Lee G., Seo B. M., Cho Y. S., et al. (2012). Dental follicle cells and cementoblasts induce apoptosis of ameloblast-lineage and Hertwig’s epithelial root sheath/epithelial rests of Malassez cells through the Fas–Fas ligand pathway. Eur. J. Oral Sci. 120 29–37. 10.1111/j.1600-0722.2011.00895.x PubMed DOI

Lesot H., Kieffer-Combeau S., Fausser J. L., Meyer J. M., Perrin-Schmitt F., Peterková R., et al. (2002). Cell-cell and cell-matrix interactions during initial enamel organ histomorphogenesis in the mouse. Connect. Tissue Res. 43 191–200. 10.1080/713713495 PubMed DOI

Lesot H., Vonesch J. L., Peterka M., Turecková J., Peterková R., Ruch J. V. (1996). Mouse molar morphogenesis revisited by three-dimensional reconstruction. II. Spatial distribution of mitoses and apoptosis in cap to bell staged first and second upper molar teeth. Int. J. Dev. Biol. 40 1017–1031. PubMed

Li J., Parada C., Chai Y. (2017). Cellular and molecular mechanisms of tooth root development. Development 144 374–384. 10.1242/dev.137216 PubMed DOI PMC

Li L., Tang Q., Nakamura T., Suh J. G., Ohshima H., Jung H. S. (2016). Fine tuning of Rac1 and RhoA alters cuspal shapes by remolding the cellular geometry. Sci. Rep. 6:37828. PubMed PMC

Li L., Yuan G., Liu C., Zhang L., Zhang Y., Chen Y., et al. (2011). Exogenous fibroblast growth factor 8 rescues development of mouse diastemal vestigial tooth ex vivo. Dev. Dyn. 240 1344–1353. 10.1002/dvdy.22596 PubMed DOI PMC

Li Y., Wang X., Ren J., Wu X., Li G., Fan Z., et al. (2018). Mandible exosomal ssc-mir-133b regulates tooth development in miniature swine via endogenous apoptosis. Bone Res. 6:28. PubMed PMC

Lindskog S., Blomlöf L., Hammarström L. (1988). Evidence for a role of odontogenic epithelium in maintaining the periodontal space. J. Clin. Periodontol. 15 371–373. 10.1111/j.1600-051x.1988.tb01014.x PubMed DOI

Little N. A., Jochemsen A. G. (2002). p63. Int. J. Biochem. Cell Biol. 34 6–9. PubMed

Liu C., Niu Y., Zhou X., Xu X., Yang Y., Zhang Y., et al. (2015). Cell cycle control, DNA damage repair, and apoptosis-related pathways control pre-ameloblasts differentiation during tooth development. BMC Genomics 16:592. 10.1186/s12864-015-1783-y PubMed DOI PMC

Liu F., Chu E. Y., Watt B., Zhang Y., Gallant N. M., Andl T., et al. (2008). Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Dev. Biol. 313 210–224. 10.1016/j.ydbio.2007.10.016 PubMed DOI PMC

Liu H., Lin H., Zhang L., Sun Q., Yuan G., Zhang L., et al. (2013). miR-145 and miR-143 regulate odontoblast differentiation through targeting Klf4 and Osx genes in a feedback loop. J. Biol. Chem. 288 9261–9271. 10.1074/jbc.m112.433730 PubMed DOI PMC

Liu W., Sun X., Braut A., Mishina Y., Behringer R. R., Mina M., et al. (2005). Distinct functions for Bmp signaling in lip and palate fusion in mice. Development 132 1453–1461. 10.1242/dev.01676 PubMed DOI

Luan X., Ito Y., Diekwisch T. G. (2006). Evolution and development of Hertwig’s epithelial root sheath. Dev. Dyn. 235 1167–1180. 10.1002/dvdy.20674 PubMed DOI PMC

Lungová V., Radlanski R. J., Tucker A. S., Renz H., Míšek I., Matalová E. (2011). Tooth-bone morphogenesis during postnatal stages of mouse first molar development. J. Anat. 218 699–716. 10.1111/j.1469-7580.2011.01367.x PubMed DOI PMC

Luukko K., Løes S., Furmanek T., Fjeld K., Kvinnsland I. H., Kettunen P. (2003). Identification of a novel putative signaling center, the tertiary enamel knot in the postnatal mouse molar tooth. Mech. Dev. 120 270–276. 10.1016/s0925-4773(02)00458-6 PubMed DOI

Manzanares E., Rasskin-Gutman D., Botella H. (2016). New insights into the enameloid microstructure of batoid fishes (Chondrichthyes). Zool. J. Linn. Soc. 177 621–632. 10.1111/zoj.12377 DOI

Marks S. C., Jr., Schroeder H. E. (1996). Tooth eruption: theories and facts. Anat. Rec. 245 374–393. 10.1002/(sici)1097-0185(199606)245:2<374::aid-ar18>3.0.co;2-m PubMed DOI

Marzetti E., Calvani R., Bernabei R., Leeuwenburgh C. (2012). Apoptosis in skeletal myocytes: a potential target for interventions against sarcopenia and physical frailty - a mini-review. Gerontology 58 99–106. PubMed PMC

Matalova E., Sharpe P. T., Lakhani S. A., Roth K. A., Flavell R. A., Setkova J., et al. (2006). Molar tooth development in caspase-3 deficient mice. Int. J. Dev. Biol. 50 491–497. PubMed

Matalova E., Witter K., Misek I. (2004). Apoptosis distribution in the first molar tooth germ of the field vole (Microtus agrestis). Tissue Cell 36 361–367. 10.1016/j.tice.2004.06.006 PubMed DOI

McIntosh J. E., Anderton X., Flores-De-Jacoby L., Carlson D. S., Shuler C. F., Diekwisch T. G. (2002). Caiman periodontium as an intermediate between basal vertebrate ankylosis-type attachment and mammalian “true” periodontium. Microsc. Res. Technol. 59 449–459. 10.1002/jemt.10222 PubMed DOI

Mizushima N., Levine B. (2010). Autophagy in mammalian development and differentiation. Nat. Cell Biol. 12 823–830. 10.1038/ncb0910-823 PubMed DOI PMC

Moe H., Jessen H. (1972). Phagocytosis and elimination of amelocyte debris by stratum intermedium cells in the trasitional zone of the enamel organ of the rat incisor. Z. Zellforsch Mikrosk Anat. 131 63–75. 10.1007/bf00307201 PubMed DOI

Moffitt K. L., Martin S. L., Walker B. (2010). From sentencing to execution–the processes of apoptosis. J. Pharm. Pharmacol. 62 547–562. 10.1211/jpp.62.05.0001 PubMed DOI

Monier B., Gettings M., Gay G., Mangeat T., Schott S., Guarner A., et al. (2015). Apico-basal forces exerted by apoptotic cells drive epithelium folding. Nature 518 245–248. 10.1038/nature14152 PubMed DOI

Montcouquiol M., Rachel R. A., Lanford P. J., Copeland N. G., Jenkins N. A., Kelley M. W. (2003). Identification of Vangl2 and Scrb1 as planar polarity genes in mammals. Nature 423 173–177. 10.1038/nature01618 PubMed DOI

Moriguchi M., Yamada M., Miake Y., Yanagisawa T. (2010). Transforming growth factor beta inducible apoptotic cascade in epithelial cells during rat molar tooth eruptions. Anat. Sci. Int. 85 92–101. 10.1007/s12565-009-0061-y PubMed DOI

Munne P. M., Tummers M., Järvinen E., Thesleff I., Jernvall J. (2009). Tinkering with the inductive mesenchyme: Sostdc1 uncovers the role of dental mesenchyme in limiting tooth induction. Development 136 393–402. 10.1242/dev.025064 PubMed DOI

Murashima-Suginami A., Takahashi K., Kawabata T., Sakata T., Tsukamoto H., Sugai M., et al. (2007). Rudiment incisors survive and erupt as supernumerary teeth as a result of USAG-1 abrogation. Biochem. Biophys. Res. Commun. 359 549–555. 10.1016/j.bbrc.2007.05.148 PubMed DOI

Muzio M. (1998). Signalling by proteolysis: death receptors induce apoptosis. Int. J. Clin. Lab. Res. 28 141–147. 10.1007/s005990050035 PubMed DOI

Nadiri A., Kuchler-Bopp S., Haikel Y., Lesot H. (2004). Immunolocalization of BMP-2/-4, FGF-4, and WNT10b in the developing mouse first lower molar. J. Histochem. Cytochem. 52 103–112. 10.1177/002215540405200110 PubMed DOI

Nadiri A., Kuchler-Bopp S., Perrin-Schmitt F., Lesot H. (2006). Expression patterns of BMPRs in the developing mouse molar. Cell Tissue Res. 324 33–40. 10.1007/s00441-005-0120-1 PubMed DOI

Nagata S. (1999). Fas ligand-induced apoptosis. Annu. Rev. Genet. 33 29–55. 10.1146/annurev.genet.33.1.29 PubMed DOI

Nair B. J. (2010). Apoptosis in odontogenesis: a brief review. Oral Maxillofac Pathol. J. 1 8–10.

Nakatsumi H., Yonehara S. (2010). Identification of functional regions defining different activity in caspase-3 and caspase-7 within cells. J. Biol. Chem. 285 25418–25425. 10.1074/jbc.m110.126573 PubMed DOI PMC

Nanci A. (2008). Ten Cate’s Oral Histology - Elsevier eBook on VitalSource, 8th Edn. Amsterdam: Elsevier.

Neupane S., Aryal Y. P., Kim T. Y., Yeon C. Y., An C. H., Kim J. Y., et al. (2020). Signaling modulations of miR-206-3p in tooth morphogenesis. Int. J. Mol. Sci. 21:5251. 10.3390/ijms21155251 PubMed DOI PMC

Nicholson D. W., Thornberry N. A. (1997). Caspases: killer proteases. Trends Biochem. Sci. 22 299–306. 10.1016/s0968-0004(97)01085-2 PubMed DOI

Nishida Y., Arakawa S., Fujitani K., Yamaguchi H., Mizuta T., Kanaseki T., et al. (2009). Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 461 654–658. 10.1038/nature08455 PubMed DOI

Nishikawa S. (2002). Colchicine-induced apoptosis and anti-Fas localization in rat-incisor ameloblasts. Anat. Sci. Int. 77 175–181. 10.1046/j.0022-7722.2002.00025.x PubMed DOI

Nishikawa S., Sasaki F. (1995). DNA localization in nuclear fragments of apoptotic ameloblasts using anti-DNA immunoelectron microscopy: programmed cell death of ameloblasts. Histochem. Cell Biol. 104 151–159. 10.1007/bf01451574 PubMed DOI

Nozue T. (1971). Specific spindle cells and globular substances in enamel knot. Okajimas Folia Anat. Jpn. 48 139–151. 10.2535/ofaj1936.48.2-3_139 PubMed DOI

Ohazama A., Johnson E. B., Ota M. S., Choi H. Y., Porntaveetus T., Oommen S., et al. (2008). Lrp4 modulates extracellular integration of cell signaling pathways in development. PLoS One 3:e4092. 10.1371/journal.pone.0004092 PubMed DOI PMC

Okai Y., Harada K., Ohura K., Arita K. (2012). Study on apoptosis in human deciduous tooth pulp cells. J. Hard Tissue Biol. 21 413–420. 10.2485/jhtb.21.413 DOI

Pantschenko A. G., Zhang W., Nahounou M., Mccarthy M. B., Stover M. L., Lichtler A. C., et al. (2005). Effect of osteoblast-targeted expression of Bcl-2 in bone: differential response in male and female mice. J. Bone Mineral Res. 20 1414–1429. 10.1359/jbmr.050315 PubMed DOI

Peterková R., Churava S., Lesot H., Rothova M., Prochazka J., Peterka M., et al. (2009). Revitalization of a diastemal tooth primordium in Spry2 null mice results from increased proliferation and decreased apoptosis. J. Exp. Zool. B Mol. Dev. Evol. 312b 292–308. 10.1002/jez.b.21266 PubMed DOI PMC

Peterková R., Lesot H., Vonesch J. L., Peterka M., Ruch J. V. (1996). Mouse molar morphogenesis revisited by three dimensional reconstruction. I. Analysis of initial stages of the first upper molar development revealed two transient buds. Int. J. Dev. Biol. 40 1009–1016. PubMed

Peterková R., Peterka M., Viriot L., Lesot H. (2000). Dentition development and budding morphogenesis. J. Craniofac. Genet. Dev. Biol. 20 158–172. PubMed

Peterková R., Peterka M., Viriot L., Lesot H. (2002). Development of the vestigial tooth primordia as part of mouse odontogenesis. Connect. Tissue Res. 43 120–128. 10.1080/713713502 PubMed DOI

Peterková R., Peterka M., Vonesch J. L., Turecková J., Viriot L., Ruch J. V., et al. (1998). Correlation between apoptosis distribution and BMP-2 and BMP-4 expression in vestigial tooth primordia in mice. Eur. J. Oral Sci. 106 667–670. 10.1046/j.0909-8836..t01-5-.x PubMed DOI

Pispa J., Jung H. S., Jernvall J., Kettunen P., Mustonen T., Tabata M. J., et al. (1999). Cusp patterning defect in Tabby mouse teeth and its partial rescue by FGF. Dev. Biol. 216 521–534. 10.1006/dbio.1999.9514 PubMed DOI

Pop C., Salvesen G. S. (2009). Human caspases: activation, specificity, and regulation. J. Biol. Chem. 284 21777–21781. 10.1074/jbc.r800084200 PubMed DOI PMC

Popa E. M., Buchtova M., Tucker A. S. (2019). Revitalising the rudimentary replacement dentition in the mouse. Development 146:dev171363. PubMed

Prochazka J., Pantalacci S., Churava S., Rothova M., Lambert A., Lesot H., et al. (2010). Patterning by heritage in mouse molar row development. Proc. Natl. Acad. Sci. U.S.A. 107 15497–15502. 10.1073/pnas.1002784107 PubMed DOI PMC

Qian H., Huang Q., Chen Y. X., Liu Q., Fang J. X., Ye M. W. (2018). Caspase-9 was involved in cell apoptosis in human dental pulp stem cells from deciduous teeth. Mol. Med. Rep. 18 1067–1073. PubMed

Rangiani A., Cao Z. G., Liu Y., Voisey Rodgers A., Jiang Y., Qin C. L., et al. (2012). Dentin matrix protein 1 and phosphate homeostasis are critical for postnatal pulp, dentin and enamel formation. Int. J. Oral Sci. 4 189–195. 10.1038/ijos.2012.69 PubMed DOI PMC

Rasch L. J., Martin K. J., Cooper R. L., Metscher B. D., Underwood C. J., Fraser G. J. (2016). An ancient dental gene set governs development and continuous regeneration of teeth in sharks. Dev. Biol. 415 347–370. 10.1016/j.ydbio.2016.01.038 PubMed DOI

Reith E. J. (1970). The stages of amelogenesis as observed in molar teeth of young rats. J. Ultrastruct. Res. 30 111–151. 10.1016/s0022-5320(70)90068-7 PubMed DOI

Reponen P., Sahlberg C., Munaut C., Thesleff I., Tryggvason K. (1994). High expression of 92-kD type IV collagenase (gelatinase B) in the osteoclast lineage during mouse development. J. Cell Biol. 124 1091–1102. 10.1083/jcb.124.6.1091 PubMed DOI PMC

Richman J. M., Handrigan G. R. (2011). Reptilian tooth development. Genesis 49 247–260. 10.1002/dvg.20721 PubMed DOI

Robinson C. (2014). Enamel maturation: a brief background with implications for some enamel dysplasias. Front. Physiol. 5:388. 10.3389/fphys.2014.00388 PubMed DOI PMC

Rodrigues L. V., Del Puerto H. L., Brant J. M., Leite R. C., Vasconcelos A. C. (2012). Caspase-3/caspase-8, bax and bcl2 in pulps of human primary teeth with physiological root resorption. Int. J. Paediatr. Dent. 22 52–59. 10.1111/j.1365-263x.2011.01157.x PubMed DOI

Rodrigues L. V., Vasconcelos A. C., Campos P. A., Brant J. M. (2009). Apoptosis in pulp elimination during physiological root resorption in human primary teeth. Braz. Dent. J. 20 179–185. 10.1590/s0103-64402009000300001 PubMed DOI

Rosfjord E. C., Dickson R. B. (1999). Growth factors, apoptosis, and survival of mammary epithelial cells. J. Mammary Gland Biol. Neoplasia 4 229–237. PubMed

Rostampour N., Appelt C. M., Abid A., Boughner J. C. (2019). Expression of new genes in vertebrate tooth development and p63 signaling. Dev. Dyn. 248 744–755. 10.1002/dvdy.26 PubMed DOI

Rubinsztein D. C., Mariño G., Kroemer G. (2011). Autophagy and aging. Cell 146 682–695. PubMed

Ruch J. V. (1985). “Epithelial-mesenchymal interactions,” in The Chemistry and Biology of Mineralized Connective Tissues, ed. Butler W. (Birminham: Ebsco Media, Inc; ), 54–62.

Sahara N., Ashizawa Y., Nakamura K., Deguchi T., Suzuki K. (1998). Ultrastructural features of odontoclasts that resorb enamel in human deciduous teeth prior to shedding. Anat. Rec. 252 215–228. 10.1002/(sici)1097-0185(199810)252:2<215::aid-ar7>3.0.co;2-1 PubMed DOI

Sahara N., Toyoki A., Ashizawa Y., Deguchi T., Suzuki K. (1996). Cytodifferentiation of the odontoclast prior to the shedding of human deciduous teeth: an ultrastructural and cytochemical study. Anat. Rec. 244 33–49. 10.1002/(sici)1097-0185(199601)244:1<33::aid-ar4>3.0.co;2-g PubMed DOI

Salomies L., Eymann J., Khan I., Di-Poï N. (2019). The alternative regenerative strategy of bearded dragon unveils the key processes underlying vertebrate tooth renewal. eLife 8:e47702. PubMed PMC

Sarkar L., Sharpe P. T. (1999). Expression of Wnt signalling pathway genes during tooth development. Mech. Dev. 85 197–200. 10.1016/s0925-4773(99)00095-7 PubMed DOI

Sasaki C., Sato T., Kozawa Y. (2001). Apoptosis in regressive deciduous tooth germs of Suncus murinus evaluated by the the TUNEL method and electron microscopy. Arch. Oral Biol. 46 649–660. 10.1016/s0003-9969(01)00007-3 PubMed DOI

Sasaki T., Ito Y., Xu X., Han J., Bringas P., Jr.,, et al. (2005). LEF1 is a critical epithelial survival factor during tooth morphogenesis. Dev. Biol. 278 130–143. 10.1016/j.ydbio.2004.10.021 PubMed DOI

Satokata I., Maas R. (1994). Msx1 deficient mice exhibit cleft palate and abnormalities of craniofacial and tooth development. Nat. Genet. 6 348–356. 10.1038/ng0494-348 PubMed DOI

Schmidt-Ullrich R., Aebischer T., Hülsken J., Birchmeier W., Klemm U., Scheidereit C. (2001). Requirement of NF-kappaB/Rel for the development of hair follicles and other epidermal appendices. Development 128 3843–3853. 10.1242/dev.128.19.3843 PubMed DOI

Schmitz I., Kirchhoff S., Krammer P. H. (2000). Regulation of death receptor-mediated apoptosis pathways. Int. J. Biochem. Cell Biol. 32 1123–1136. 10.1016/s1357-2725(00)00048-0 PubMed DOI

Setkova J., Lesot H., Matalova E., Witter K., Matulova P., Misek I. (2006). Proliferation and apoptosis in early molar morphogenesis– voles as models in odontogenesis. Int. J. Dev. Biol. 50 481–489. PubMed

Setkova J., Matalova E., Sharpe P. T., Misek I., Tucker A. S. (2007). Primary enamel knot cell death in Apaf-1 and caspase-9 deficient mice. Arch. Oral. Biol. 52 15–19. 10.1016/j.archoralbio.2006.07.006 PubMed DOI

Shaw J. P. (1979). The time scale of tooth development and replacement in Xenopus laevis (Daudin). J. Anat. 129 323–342. PubMed PMC

Shibata S., Suzuki S., Tengan T., Yamashita Y. (1995). A histochemical study of apoptosis in the reduced ameloblasts of erupting mouse molars. Arch. Oral Biol. 40 677–680. 10.1016/0003-9969(95)00021-g PubMed DOI

Shigehara N. (1980). Epiphyseal union and tooth eruption of the Ryukyu house shrew, Suncus murinus, in captivity. J. Mamm. Soc. Jpn. 8 151–159.

Shigemura N., Kiyoshima T., Kobayashi I., Matsuo K., Yamaza H., Akamine A., et al. (1999). The distribution of BrdU- and TUNEL-positive cells during odontogenesis in mouse lower first molars. Histochem. J. 31 367–377. PubMed

Shigemura N., Kiyoshima T., Sakai T., Matsuo K., Momoi T., Yamaza H., et al. (2001). Localization of activated caspase-3-positive and apoptotic cells in the developing tooth germ of the mouse lower first molar. Histochem. J. 33 253–258. PubMed

Siegel R. M., Chan F. K., Chun H. J., Lenardo M. J. (2000). The multifaceted role of Fas signaling in immune cell homeostasis and autoimmunity. Nat. Immunol. 1 469–474. 10.1038/82712 PubMed DOI

Simpson H. E. (1965). The degeneration of the rests of malassez with age as observed by the apoxestic technique. J. Periodontol. 36 288–291. 10.1902/jop.1965.36.4.288 PubMed DOI

Slootweg P. J., De Weger R. A. (1994). Immunohistochemical demonstration of bcl-2 protein in human tooth germs. Arch. Oral Biol. 39 545–550. 10.1016/0003-9969(94)90129-5 PubMed DOI

Smith C. E. (1998). Cellular and chemical events during enamel maturation. Crit. Rev. Oral Biol. Med. 9 128–161. 10.1177/10454411980090020101 PubMed DOI

Smith C. E., Nanci A. (1995). Overview of morphological changes in enamel organ cells associated with major events in amelogenesis. Int. J. Dev. Biol. 39 153–161. PubMed

Smith C. E., Warshawsky H. (1977). Quantitative analysis of cell turnover in the enamel organ of the rat incisor. Evidence for ameloblast death immediately after enamel matrix secretion. Anat. Rec. 187 63–98. 10.1002/ar.1091870106 PubMed DOI

Sonoyama W., Seo B. M., Yamaza T., Shi S. (2007). Human Hertwig’s epithelial root sheath cells play crucial roles in cementum formation. J. Dent. Res. 86 594–599. 10.1177/154405910708600703 PubMed DOI

Srivastava A. K., Pispa J., Hartung A. J., Du Y., Ezer S., Jenks T., et al. (1997). The Tabby phenotype is caused by mutation in a mouse homologue of the EDA gene that reveals novel mouse and human exons and encodes a protein (ectodysplasin-A) with collagenous domains. Proc. Natl. Acad. Sci. U.S.A. 94 13069–13074. 10.1073/pnas.94.24.13069 PubMed DOI PMC

Stock D. W., Weiss K. M., Zhao Z. (1997). Patterning of the mammalian dentition in development and evolution. Bioessays 19 481–490. 10.1002/bies.950190607 PubMed DOI

Strasser A., O’connor L., Dixit V. M. (2000). Apoptosis signaling. Annu. Rev. Biochem. 69 217–245. PubMed

Susin S. A., Lorenzo H. K., Zamzami N., Marzo I., Snow B. E., Brothers G. M., et al. (1999). Molecular characterization of mitochondrial apoptosis-inducing factor. Nature 397 441–446. PubMed

Suzuki M., Inoue T., Shimono M., Yamada S. (2002). Behavior of epithelial root sheath during tooth root formation in porcine molars: TUNEL, TEM, and immunohistochemical studies. Anat. Embryol. 206 13–20. 10.1007/s00429-002-0276-3 PubMed DOI

Svandova E., Vesela B., Tucker A. S., Matalova E. (2018). Activation of pro-apoptotic caspases in non-apoptotic cells during odontogenesis and related osteogenesis. Front. Physiol. 9:174. 10.3389/fphys.2018.00174 PubMed DOI PMC

Terman A., Brunk U. T. (2005). Autophagy in cardiac myocyte homeostasis, aging, and pathology. Cardiovasc. Res. 68 355–365. 10.1016/j.cardiores.2005.08.014 PubMed DOI

Terman A., Gustafsson B., Brunk U. T. (2007). Autophagy, organelles and ageing. J. Pathol. 211 134–143. 10.1002/path.2094 PubMed DOI

Thesleff I. (2003). Epithelial-mesenchymal signalling regulating tooth morphogenesis. J. Cell Sci. 116 1647–1648. 10.1242/jcs.00410 PubMed DOI

Thesleff I., Keränen S., Jernvall J. (2001). Enamel knots as signaling centers linking tooth morphogenesis and odontoblast differentiation. Adv. Dent. Res. 15 14–18. 10.1177/08959374010150010401 PubMed DOI

Thomas B. L., Tucker A. S., Qui M., Ferguson C. A., Hardcastle Z., Rubenstein J. L., et al. (1997). Role of Dlx-1 and Dlx-2 genes in patterning of the murine dentition. Development 124 4811–4818. 10.1242/dev.124.23.4811 PubMed DOI

Tsuchiya M., Sharma R., Tye C. E., Sugiyama T., Bartlett J. D. (2009). Transforming growth factor-beta1 expression is up-regulated in maturation-stage enamel organ and may induce ameloblast apoptosis. Eur. J. Oral Sci. 117 105–112. 10.1111/j.1600-0722.2009.00612.x PubMed DOI PMC

Tucker A. S., Fraser G. J. (2014). Evolution and developmental diversity of tooth regeneration. Semin. Cell Dev. Biol. 25-26 71–80. 10.1016/j.semcdb.2013.12.013 PubMed DOI

Tummers B., Green D. R. (2017). Caspase-8: regulating life and death. Immunol. Rev. 277 76–89. 10.1111/imr.12541 PubMed DOI PMC

Turecková J., Lesot H., Vonesch J. L., Peterka M., Peterkova R., Ruch J. V. (1996). Apoptosis is involved in the disappearance of the diastemal dental primordia in mouse embryo. Int. J. Dev. Biol. 40 483–489. PubMed

Vaahtokari A., Aberg T., Thesleff I. (1996). Apoptosis in the developing tooth: association with an embryonic signaling center and suppression by EGF and FGF-4. Development 122 121–129. 10.1242/dev.122.1.121 PubMed DOI

van Genderen C., Okamura R. M., Fariñas I., Quo R. G., Parslow T. G., Bruhn L., et al. (1994). Development of several organs that require inductive epithelial-mesenchymal interactions is impaired in LEF-1-deficient mice. Genes Dev. 8 2691–2703. 10.1101/gad.8.22.2691 PubMed DOI

Varfolomeev E. E., Schuchmann M., Luria V., Chiannilkulchai N., Beckmann J. S., Mett I. L., et al. (1998). Targeted disruption of the mouse Caspase 8 gene ablates cell death induction by the TNF receptors, Fas/Apo1, and DR3 and is lethal prenatally. Immunity 9 267–276. 10.1016/s1074-7613(00)80609-3 PubMed DOI

Vellai T. (2009). Autophagy genes and ageing. Cell Death Differ. 16 94–102. 10.1038/cdd.2008.126 PubMed DOI

Vermelin L., Lécolle S., Septier D., Lasfargues J. J., Goldberg M. (1996). Apoptosis in human and rat dental pulp. Eur. J. Oral Sci. 104 547–553. 10.1111/j.1600-0722.1996.tb00140.x PubMed DOI

Viriot L., Lesot H., Vonesch J. L., Ruch J. V., Peterka M., Peterková R. (2000). The presence of rudimentary odontogenic structures in the mouse embryonic mandible requires reinterpretation of developmental control of first lower molar histomorphogenesis. Int. J. Dev. Biol. 44 233–240. PubMed

Walsh J. G., Cullen S. P., Sheridan C., Lüthi A. U., Gerner C., Martin S. J. (2008). Executioner caspase-3 and caspase-7 are functionally distinct proteases. Proc. Natl. Acad. Sci. U.S.A. 105 12815–12819. 10.1073/pnas.0707715105 PubMed DOI PMC

Warner S. J., Yashiro H., Longmore G. D. (2010). The Cdc42/Par6/aPKC polarity complex regulates apoptosis-induced compensatory proliferation in epithelia. Curr. Biol. 20 677–686. 10.1016/j.cub.2010.03.025 PubMed DOI PMC

Warshawsky H., Josephsen K., Thylstrup A., Fejerskov O. (1981). The development of enamel structure in rat incisors as compared to the teeth of monkey and man. Anat. Rec. 200 371–399. 10.1002/ar.1092000402 PubMed DOI

Wautier K., Van Der Heyden C., Huysseune A. (2001). A quantitative analysis of pharyngeal tooth shape in the zebrafish (Danio rerio, Teleostei, Cyprinidae). Arch. Oral. Biol. 46 67–75. 10.1016/s0003-9969(00)00091-1 PubMed DOI

Wesselink P. R., Beertsen W. (1993). The prevalence and distribution of rests of Malassez in the mouse molar and their possible role in repair and maintenance of the periodontal ligament. Arch. Oral Biol. 38 399–403. 10.1016/0003-9969(93)90211-4 PubMed DOI

Westergaard B., Ferguson M. W. (1986). Development of the dentition in Alligator mississipiensis. Early embryonic development in the lower jaw. J. Zool. 210 575–597. 10.1111/j.1469-7998.1986.tb03657.x DOI

Westergaard B., Ferguson M. W. J. (1987). Development of the dentition in Alligator mississippiensis. Later development in the lower jaws of embryos, hatchlings and young juveniles. J. Zool. 212 191–222. 10.1111/j.1469-7998.1987.tb05984.x PubMed DOI

Whitlock J. A., Richman J. M. (2013). Biology of tooth replacement in amniotes. Int. J. Oral Sci. 5 66–70. 10.1038/ijos.2013.36 PubMed DOI PMC

Wirawan E., Vande Walle L., Kersse K., Cornelis S., Claerhout S., Vanoverberghe I., et al. (2010). Caspase-mediated cleavage of Beclin-1 inactivates Beclin-1-induced autophagy and enhances apoptosis by promoting the release of proapoptotic factors from mitochondria. Cell Death Dis. 1:e18. 10.1038/cddis.2009.16 PubMed DOI PMC

Wistuba J., Greven H., Clemen G. (2002). Development of larval and transformed teeth in Ambystoma mexicanum (Urodela, Amphibia): an ultrastructural study. Tissue Cell 34 14–27. 10.1054/tice.2002.0219 PubMed DOI

Woltgens J. H., Lyaruu D. M., Bervoets T. J., Bronckers A. L. (1987). Effects of calcium and phosphate on secretion of enamel matrix and its subsequent mineralization in vitro. Adv. Dent. Res. 1 196–201. 10.1177/08959374870010020801 PubMed DOI

Wu C. C., Lee S., Malladi S., Chen M. D., Mastrandrea N. J., Zhang Z., et al. (2016). The Apaf-1 apoptosome induces formation of caspase-9 homo- and heterodimers with distinct activities. Nat. Commun. 7:13565. PubMed PMC

Wu P., Wu X., Jiang T. X., Elsey R. M., Temple B. L., Divers S. J., et al. (2013). Specialized stem cell niche enables repetitive renewal of alligator teeth. Proc. Natl. Acad. Sci. U.S.A. 110 E2009–E2018. PubMed PMC

Wu Z., Epasinghe D. J., He J., Li L., Green D. W., Lee M. J., et al. (2016). Altered tooth morphogenesis after silencing the planar cell polarity core component, Vangl2. Cell Tissue Res. 366 617–621. 10.1007/s00441-016-2489-4 PubMed DOI

Yamamoto H., Cho S. W., Song S. J., Hwang H. J., Lee M. J., Kim J. Y., et al. (2005). Characteristic tissue interaction of the diastema region in mice. Arch. Oral Biol. 50 189–198. 10.1016/j.archoralbio.2004.11.010 PubMed DOI

Yamamoto T., Yamamoto T., Yamada T., Hasegawa T., Hongo H., Oda K., et al. (2014). Hertwig’s epithelial root sheath cell behavior during initial acellular cementogenesis in rat molars. Histochem. Cell Biol. 142 489–496. 10.1007/s00418-014-1230-1 PubMed DOI

Yamanaka A., Yasui K., Sonomura T., Iwai H., Uemura M. (2010). Development of deciduous and permanent dentitions in the upper jaw of the house shrew (Suncus murinus). Arch. Oral Biol. 55 279–287. 10.1016/j.archoralbio.2010.02.006 PubMed DOI

Yang J., Wan C., Nie S., Jian S., Sun Z., Zhang L., et al. (2013). Localization of Beclin1 in mouse developing tooth germs: possible implication of the interrelation between autophagy and apoptosis. J. Mol. Histol. 44 619–627. 10.1007/s10735-013-9518-3 PubMed DOI

Yang J. W., Zhu L. X., Yuan G. H., Chen Y. X., Zhang L., Zhang L., et al. (2013). Autophagy appears during the development of the mouse lower first molar. Histochem. Cell Biol. 139 109–118. 10.1007/s00418-012-1016-2 PubMed DOI

Ye L., Macdougall M., Zhang S., Xie Y., Zhang J., Li Z., et al. (2004). Deletion of dentin matrix protein-1 leads to a partial failure of maturation of predentin into dentin, hypomineralization, and expanded cavities of pulp and root canal during postnatal tooth development. J. Biol. Chem. 279 19141–19148. 10.1074/jbc.m400490200 PubMed DOI

Ye L., Mishina Y., Chen D., Huang H., Dallas S. L., Dallas M. R., et al. (2005). Dmp1-deficient mice display severe defects in cartilage formation responsible for a chondrodysplasia-like phenotype. J. Biol. Chem. 280 6197–6203. 10.1074/jbc.m412911200 PubMed DOI PMC

Yoshioka C., Muraki Y., Fukuda J., Haneji T., Kobayashi N. (1996). Identification of the Fas antigen in human gingiva. J. Dent. Res. 75 1353–1357. 10.1177/00220345960750060501 PubMed DOI

Youle R. J., Karbowski M. (2005). Mitochondrial fission in apoptosis. Nat. Rev. Mol. Cell Biol. 6 657–663. PubMed

Youle R. J., Strasser A. (2008). The BCL-2 protein family: opposing activities that mediate cell death. Nat. Rev. Mol. Cell Biol. 9 47–59. 10.1038/nrm2308 PubMed DOI

Yu J. C., Fox Z. D., Crimp J. L., Littleford H. E., Jowdry A. L., Jackman W. R. (2015). Hedgehog signaling regulates dental papilla formation and tooth size during zebrafish odontogenesis. Dev. Dyn. 244 577–590. 10.1002/dvdy.24258 PubMed DOI PMC

Zahradnicek O., Horacek I., Tucker A. S. (2008). Viperous fangs: development and evolution of the venom canal. Mech. Dev. 125 786–796. 10.1016/j.mod.2008.06.008 PubMed DOI

Zahradnicek O., Horacek I., Tucker A. S. (2012). Tooth development in a model reptile: functional and null generation teeth in the gecko Paroedura picta. J. Anat. 221 195–208. 10.1111/j.1469-7580.2012.01531.x PubMed DOI PMC

Zaki A. E., MacRae E. K. (1977). Fine structure of the secretory and nonsecretory ameloblasts in the frog. I. Fine structure of the secretory ameloblasts. Am. J. Anat. 148 161–193. 10.1002/aja.1001480202 PubMed DOI

Zaki A. E., MacRae E. K. (1978). Fine structure of the secretory and non-secretory ameloblasts in the frog. II. Fine structure of the non-secretory ameloblast. J. Morphol. 158 181–197. 10.1002/jmor.1051580205 PubMed DOI

Zhang L., Chen Z. (2015). “Role of autophagy and apoptosis in odontogenesis,” in Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, ed. Hayat M. A. (Cambridge, MA: Academic Press; ), 183–193. 10.1016/b978-0-12-801043-3.00011-x DOI

Zhang Q., Major M. B., Takanashi S., Camp N. D., Nishiya N., Peters E. C., et al. (2007). Small-molecule synergist of the Wnt/beta-catenin signaling pathway. Proc. Natl. Acad. Sci. U.S.A. 104 7444–7448. 10.1073/pnas.0702136104 PubMed DOI PMC

Zhang W., Ju J., Gronowicz G. (2010). Odontoblast-targeted Bcl-2 overexpression impairs dentin formation. J. Cell. Biochem. 111 425–432. 10.1002/jcb.22722 PubMed DOI PMC

Zimmermann K. C., Bonzon C., Green D. R. (2001). The machinery of programmed cell death. Pharmacol. Ther. 92 57–70. PubMed

Zur Nieden N. I., Kempka G., Ahr H. J. (2003). In vitro differentiation of embryonic stem cells into mineralized osteoblasts. Differentiation 71 18–27. 10.1046/j.1432-0436.2003.700602.x PubMed DOI