In past decades, morphologic, molecular, and cellular mechanisms that govern tooth development have been extensively studied. These studies demonstrated that the same signaling pathways regulate development of the primary and successional teeth. Mutations of these pathways lead to abnormalities in tooth development and number, including aberrant tooth shape, tooth agenesis, and formation of extra teeth. Here, we summarize the current knowledge on the development of the primary and successional teeth in animal models and describe some of the common tooth abnormalities in humans.
AdaimyLChoueryEMegarbaneHMrouehSDelagueVNicolasEBelguithHde MazancourtPMegarbaneA. 2007. Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odonto-onycho-dermal dysplasia. Am J Hum Genet. 81(4):821–828.
2.
AhnYSandersonBWKleinODKrumlaufR. 2010. Inhibition of Wnt signaling by Wise (Sostdc1) and negative feedback from Shh controls tooth number and patterning. Development. 137(19):3221–3231.
3.
AhtiainenLUskiIThesleffIMikkolaML. 2016. Early epithelial signaling center governs tooth budding morphogenesis. J Cell Biol. 214(6):753–767.
4.
ArteSParmanenSPirinenSAlaluusuaSNieminenP. 2013. Candidate gene analysis of tooth agenesis identifies novel mutations in six genes and suggests significant role for WNT and EDA signaling and allele combinations. PLoS One. 8(8):e73705.
5.
ArzooPSKlarJBergendalBNorderydJDahlN. 2014. Wnt10a mutations account for (1/4) of population-based isolated oligodontia and show phenotypic correlations. Am J Med Genet A. 164(2):353–359.
6.
BalicAThesleffI. 2015. Tissue interactions regulating tooth development and renewal. Curr Top Dev Biol. 115:157–186.
7.
BergendalBNorderydJZhouXKlarJDahlN. 2016. Abnormal primary and permanent dentitions with ectodermal symptoms predict WNT10A deficiency. BMC Med Genet. 17(1):88.
8.
Bloch-ZupanAJametXEtardCLaugelVMullerJGeoffroyVStraussJPPelletierVMarionVPochOet al. 2011. Homozygosity mapping and candidate prioritization identify mutations, missed by whole-exome sequencing, in SMOC2, causing major dental developmental defects. Am J Hum Genet. 89(6):773–781.
9.
BrookAHJernvallJSmithRNHughesTETownsendGC. 2014. The dentition: the outcomes of morphogenesis leading to variations of tooth number, size and shape. Aust Dent J. 59 Suppl1:131–142.
CarterKWorthingtonS. 2015. Morphologic and demographic predictors of third molar agenesis: a systematic review and meta-analysis. J Dent Res. 94(7):886–894.
12.
CluzeauCHadj-RabiaSJambouMMansourSGuiguePMasmoudiSBalEChassaingNVincentMCViotGet al. 2011. Only four genes (EDA1, EDAR, EDARADD, and WNT10A) account for 90% of hypohidrotic/anhidrotic ectodermal dysplasia cases. Hum Mutat. 32(1):70–72.
13.
GaeteMTuckerAS. 2013. Organized emergence of multiple-generations of teeth in snakes is dysregulated by activation of Wnt/beta-catenin signalling. PLoS One. 8(9):e74484.
14.
HandriganGRLeungKJRichmanJM. 2010. Identification of putative dental epithelial stem cells in a lizard with life-long tooth replacement. Development. 137(21):3545–3549.
15.
HandriganGRRichmanJM. 2010. A network of Wnt, hedgehog and BMP signaling pathways regulates tooth replacement in snakes. Dev Biol. 348(1):130–141.
16.
HovorakovaMLesotHPeterkovaRPeterkaM. 2006. Origin of the deciduous upper lateral incisor and its clinical aspects. J Dent Res. 85(2):167–171.
17.
HovorakovaMLesotHVoneschJLPeterkaMPeterkovaR. 2007. Early development of the lower deciduous dentition and oral vestibule in human embryos. Eur J Oral Sci. 115(4):280–287.
18.
HuysseuneAWittenPE. 2006. Developmental mechanisms underlying tooth patterning in continuously replacing osteichthyan dentitions. J Exp Zool B Mol Dev Evol. 306(3):204–215.
19.
JärvinenESalazar-CiudadIBirchmeierWTaketoMMJernvallJThesleffI. 2006. Continuous tooth generation in mouse is induced by activated epithelial Wnt/beta-catenin signaling. Proc Natl Acad Sci U S A. 103(49):18627–18632.
20.
JärvinenETummersMThesleffI. 2009. The role of the dental lamina in mammalian tooth replacement. J Exp Zool B Mol Dev Evol. 312(4):281–291.
21.
JärvinenEValimakiKPummilaMThesleffIJernvallJ. 2008. The taming of the shrew milk teeth. Evol Dev. 10(4):477–486.
22.
JensenBLKreiborgS. 1990. Development of the dentition in cleidocranial dysplasia. J Oral Pathol Med. 19(2):89–93.
23.
JernvallJThesleffI. 2012. Tooth shape formation and tooth renewal: evolving with the same signals. Development. 139(19):3487–3497.
24.
JumlongrasDBeiMStimsonJMWangWFDePalmaSRSeidmanCEFelborUMaasRSeidmanJGOlsenBR. 2001. A nonsense mutation in MSX1 causes Witkop syndrome. Am J Hum Genet. 69(1):67–74.
25.
JussilaMCrespo YanezXThesleffI. 2014. Initiation of teeth from the dental lamina in the ferret. Differentiation. 87(1–2):32–43.
26.
JuuriEJussilaMSeidelKHolmesSWuPRichmanJHeikinheimoKChuongCMArnoldKHochedlingerKet al. 2013. Sox2 marks epithelial competence to generate teeth in mammals and reptiles. Development. 140(7):1424–1432.
LammiLArteSSomerMJarvinenHLahermoPThesleffIPirinenSNieminenP. 2004. Mutations in AXIN2 cause familial tooth agenesis and predispose to colorectal cancer. Am J Hum Genet. 74(5):1043–1050.
29.
LaurikkalaJMikkolaMLJamesMTummersMMillsAAThesleffI. 2006. P63 regulates multiple signalling pathways required for ectodermal organogenesis and differentiation. Development. 133(8):1553–1563.
30.
LiuFChuEYWattBZhangYGallantNMAndlTYangSHLuMMPiccoloSSchmidt-UllrichRet al. 2008. Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Dev Biol. 313(1):210–224.
31.
MartinKJRaschLJCooperRLMetscherBDJohansonZFraserGJ. 2016. Sox2+ progenitors in sharks link taste development with the evolution of regenerative teeth from denticles. Proc Natl Acad Sci U S A. 113(51):14769–14774.
32.
MassinkMPCretonMASpanevelloFFennisWMCuneMSSavelbergSMNijmanIJMauriceMMvan den BoogaardMJvan HaaftenG. 2015. Loss-of-function mutations in the WNT co-receptor LRP6 cause autosomal-dominant oligodontia. Am J Hum Genet. 97(4):621–626.
MuesGBondsJXiangLVieiraARSeymenFKleinOD’SouzaRN. 2014. The WNT10A gene in ectodermal dysplasias and selective tooth agenesis. Am J Med Genet A. 164(10):2455–2460.
35.
MunnePMTummersMJarvinenEThesleffIJernvallJ. 2009. Tinkering with the inductive mesenchyme: Sostdc1 uncovers the role of dental mesenchyme in limiting tooth induction. Development. 136(3):393–402.
36.
MustonenTPispaJMikkolaMLPummilaMKangasATPakkasjarviLJaatinenRThesleffI. 2003. Stimulation of ectodermal organ development by Ectodysplasin-A1. Dev Biol. 259(1):123–136.
37.
NakamuraTUndaFde-VegaSVilaxaAFukumotoSYamadaKMYamadaY. 2004. The Krüppel-like factor epiprofin is expressed by epithelium of developing teeth, hair follicles, and limb buds and promotes cell proliferation. J Biol Chem. 279(1):626–634.
38.
NieminenP. 2009. Genetic basis of tooth agenesis. J Exp Zool B Mol Dev Evol. 312(4):320–342.
39.
NieminenPMorganNVFenwickALParmanenSVeistinenLMikkolaMLvan der SpekPJGiraudAJuddLArteSet al. 2011. Inactivation of IL11 signaling causes craniosynostosis, delayed tooth eruption, and supernumerary teeth. Am J Hum Genet. 89(1):67–81.
40.
NoorAWindpassingerCVitcuIOrlicMRafiqMAKhalidMMalikMNAyubMAlmanBVincentJB. 2009. Oligodontia is caused by mutation in LTBP3, the gene encoding latent TGF-beta binding protein 3. Am J Hum Genet. 84(4):519–523.
41.
NumakuraCKitanakaSKatoMIshikawaSHamamotoYKatsushimaYKimuraTHayasakaK. 2010. Supernumerary impacted teeth in a patient with SOX2 anophthalmia syndrome. Am J Med Genet A. 152(9):2355–2359.
42.
OoëT. 1981. Human tooth and dental arch development. Tokyo (Japan): Ishiyaku Publishers Inc.
43.
PeterkovaRHovorakovaMPeterkaMLesotH. 2014. Three-dimensional analysis of the early development of the dentition. Aust Dent J. 59 Suppl1:55–80.
44.
PispaJJungHSJernvallJKettunenPMustonenTTabataMJKereJThesleffI. 1999. Cusp patterning defect in tabby mouse teeth and its partial rescue by FGF. Dev Biol. 216(2):521–534.
45.
PopaEMAnthwalNTuckerAS. 2016. Complex patterns of tooth replacement revealed in the fruit bat (Eidolon helvum). J Anat. 229(6):847–856.
46.
PutnovaIDosedelovaHBryjaVLandovaMBuchtovaMStembirekJ. 2017. Angled growth of the dental lamina is accompanied by asymmetrical expression of the WNT pathway receptor frizzled 6. Front Physiol. 8:29.
47.
PuttalingaiahVDAgarwalPMiglaniRGuptaPSankaranADubeG. 2014. Assessing the association of taurodontism with numeric dentition anomalies in an adult central indian population. J Nat Sci Biol Med. 5(2):429–433.
SchinzelAKlauslerM. 1986. The Van der Woude syndrome (dominantly inherited lip pits and clefts). J Med Genet. 23(4):291–294.
50.
SeminaEVReiterRLeysensNJAlwardWLSmallKWDatsonNASiegel-BarteltJBierke-NelsonDBitounPZabelBUet al. 1996. Cloning and characterization of a novel bicoid-related homeobox transcription factor gene, RIEG, involved in Rieger syndrome. Nat Genet. 14(4):392–399.
51.
StembírekJBuchtováMKrálTMatalováELozanoffSMíšekI. 2010. Early morphogenesis of heterodont dentition in minipigs. Eur J Oral Sci. 118(6):547–558.
52.
StocktonDWDasPGoldenbergMD’SouzaRNPatelPI. 2000. Mutation of PAX9 is associated with oligodontia. Nat Genet. 24(1):18–19.
53.
Van BuggenhoutGBailleul-ForestierI. 2008. Mesiodens. Eur J Med Genet. 51(2):178–181.
54.
VastardisHKarimbuxNGuthuaSWSeidmanJGSeidmanCE. 1996. A human MSX1 homeodomain missense mutation causes selective tooth agenesis. Nat Genet. 13(4):417–421.
55.
WangXPAbergTJamesMJLevanonDGronerYThesleffI. 2005. Runx2 (Cbfa1) inhibits Shh signaling in the lower but not upper molars of mouse embryos and prevents the budding of putative successional teeth. J Dent Res. 84(2):138–143.
56.
WangXPFanJ. 2011. Molecular genetics of supernumerary tooth formation. Genesis. 49(4):261–277.
57.
WangXPO’ConnellDJLundJJSaadiIKuraguchiMTurbe-DoanACavallescoRKimHParkPJHaradaHet al. 2009. Apc inhibition of Wnt signaling regulates supernumerary tooth formation during embryogenesis and throughout adulthood. Development. 136(11):1939–1949.
58.
YangJWangSKChoiMReidBMHuYLeeYLHerzogCRKim-BermanHLeeMBenkePJet al. 2015. Taurodontism, variations in tooth number, and misshapened crowns in Wnt10a null mice and human kindreds. Mol Genet Genomic Med. 3(1):40–58.
ZhangZLanYChaiYJiangR. 2009. Antagonistic actions of Msx1 and Osr2 pattern mammalian teeth into a single row. Science. 323(5918):1232–1234.
61.
ZonanaJElderMESchneiderLCOrlowSJMossCGolabiMShapiraSKFarndonPAWaraDWEmmalSAet al. 2000. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet. 67(6):1555–1562.
