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1、UnitTwelveDEVELOPMENTBIOLOGYOFENAMELTounderstandhowmolecularbiologistsareattackingtheproblemofinheriteddisordersofenamel,abriefreviewofdentalembryologyisneeded.Theearlystagesoftoothdevelopmentarecharacterizedbyabuddingoffofepitheliumfromtheoralepitheliumitselfintotheareaofthefuturealveolarbone.Thist
2、oothprecursorwillgiverisetobothprimaryandpermanentdentitionsinthearea(incisor,premolar,etc.).Onlytheinnerlayerofthedoublelayerofcells(theinnerenamelepithelium)hasafunctionaltoothfate-itgivesrisetotheenamel.Thesequenceinwhichthisoccursisnowwelldocumentedandprovidesanexcellentexampleofhowembryonictiss
3、uesdifferentiateundertheinfluenceofadjacentbutdevelopmentallydifferentcells.Inthiscase,neuralcrestcellsmigratingintothedeniallaminaareafromaroundthedevelopingneurallubecametolieinanintimatebutnottouchingrelationshipnexttotheinnerenamelepithelium.Thetwodevelopmentallydifferentcelllayers(innerenamelep
4、itheliumenameljandtheneuralcrestdentin)areseparatedbyanextracellularmatrix,theECM.Thesequenceofmoleculareventsleadingtoenamelformationmaybesummarizedasfollows:1. Neuralcrestcellssecreteanenamel-inducingsubstancethatmigratesacross(heinterveningmatrix(ECM)asamatrixvesicleandmakescontactwiththeinnerena
5、melepithelium(IEE).2. Thisenamel-inducingsubstancepenetratestheIEEcellandactivatesthatcelltobeginproducingitsorganicenamelmatrix.3. Thefutureenamelcell(pieamloblast)inturnsendsadifferentorganicmolecule(message)backacrossthematrixtotheneuralcrestcells(preodontoblasts)whereitsignalsthesecellstoinitiat
6、ethefullscaleproductionofdentin.4. Thematricesofbothcelltypes(ameloblastandodontoblast)consistofspecificproteins(hatwillultimatelycalcifyintoenamel,whichismuchharderthandentin.Molecularbiologistsworkinginthisarearecognizetwoproteinsinenamel(amelogeninandenamelin)andaphosphoproteinindentin.Tobeconsis
7、tentwithcurrentgeneticconcepts,wepresumethatalltheinheriteddefectsofenamelcanbetracedtoDNAalterations(mutations)thatwillresultinerrorsineitheroneorbothoftheseproteins.Themostintriguingdentalresearchtodayis1)theattempttolocalizethegenesfortheseproteinstoagivenchromosomeand2)thebiochemicalidentificati
8、onofspecificdefectintheprotein(hatpreventsitformfunctioningnormally.Thefollowingisadiscussionofgeneticprinciplesbestexemplifiedbytheheritabledisordersofenamel.Basedupontheclinicalappearance,radiographiccharacteristicsandmicroscopicfeatures,oralpathologistshaverecognizedthreemajortypesofinheritedenam
9、eldefects:hypoplasia,hypocalcificationandhypomaturation.Thesetermsalsoprovideuswiththegeneraldescriptionofthediseasephenotypes.Forexample,intype1,enamelhypoplasia,theenamelishard,wellcalcifiedbutdefectiveinamount.Twotypesofdeficientenamelphenotypesarcseen:generalized(alltheenamel)andlocalized(pitsan
10、dgroovesinspecificareas).Type2,hypocalcification.Disordersarethoseinwhichtheenamelmatrixissodrasticallyaltered,thatnormalcalcificationcannotoccur,withtheresult(ha(heclinicalphenotypeisasoft,mushyenamelthateasilywearsaway.Type3defect,hypomaturation,involvestheprocessofmaturationoftheenamelcrystal.Thi
11、soccursafteranessentiallynormalenamelmatrixhasbeenestablished.Theenamelisofnormalthickness(nothypoplastic)andrelativelynormalhardness(slightlyhypocalcified)withreducedradiographicdensityanddiscoloration.Fromthiscollectionofenameldiseasewecannowdrawoutfourexamplesofamelogenesisimperfecta(atleast10dif
12、ferenttypesrecognized)thatillustratethefourmajorMendclianmodesofinheritance:autosomaldominant(AD)andautosomalrecessive(AR);X-linkeddominant(XLD)andX-linkedrecessive(XLR).Onecharacteristicofinheriteddentaldefectsisthatbothdentitions(primaryandpermanent)mustbeaffected.Occasionally,thedefectisexpressed
13、differentlyinthedentitions,asinthecaseofdentindysplasiatypeII.However,itismuchmorecommontoseethesameclinicalandradiographicpictureinbothdentitions.Theamelogenesisimperfectasalwaysshowbothdentitionsaffected.VOCABULARY1. dentalembryologyincisor2. premolarepithelium3. differentiateneuralcrestcell4. mig
14、ratedentallamina5. preameloblastpreodontoblast6. phosphoproteinalteration(mutation)7. intriguingchromosome8. hypoplasiahypocalcificaiion9. hypomaturationdiseasephenotype10. amelgenesisimperfectaMendelianinheritance11. autosomaldominant(AD)autosomalrecessive(AR)12. X-linkeddominated(XLR)X-linkedrecessive(XLR)13. dentindysplasiaaniclogcnin14. enamelindentitions牙胚胎学切牙双尖牙上皮分化神经脊细胞移出牙板前期成釉细胞前期成牙本质细胞磷酸蛋白交替有意义的，有趣的染色体发育不良钙化不良成熟不足疾病表现型釉质发育不全孟德尔遗传常染色体显性常染色体隐性性染色体显性性染色体隐性牙本质发育不良成釉蛋白釉蛋白牙列内釉上皮15. innerenamelepithelium(IEE)
