The old and new face of craniofacial research: How animal models inform human craniofacial genetic and clinical data

摘要

Thecraniofacialskeletalstructuresthatcomprisethehumanheaddevelopfrommultipletissuesthatconvergetoformthebonesandcartilageoftheface.Becauseoftheircomplexdevelopmentandmorphogenesis,manyhumanbirthdefectsariseduetodisruptionsinthesecellularpopulations.Thus,determininghowthesestructuresnormallydevelopisvitalifwearetogainadeeperunderstandingofcraniofacialbirthdefectsanddevisetreatmentandpreventionoptions.Inthisreview,wewillfocusonhowanimalmodelsystemshavebeenusedhistoricallyandinanongoingcontexttoenhanceourunderstandingofhumancraniofacialdevelopment.Wedothisbyfirsthighlightingldquo;animaltomanrdquo;approaches;thatis,howanimalmodelsarebeingutilizedtounderstandfundamentalmechanismsofcraniofacialdevelopment.Wediscussemergingtechnologies,includinghighthroughputsequencingandgenomeediting,andnewanimalrepositoryresources,andhowtheirapplicationcanrevolutionizethefutureofanimalmodelsincraniofacialresearch.Secondly,wehighlightldquo;mantoanimalrdquo;approaches,includingthecurrentuseofanimalmodelstotestthefunctionofcandidatehumandiseasevariants.Specifically,weoutlineacommonworkflowdeployedafterdiscoveryofapotentiallydiseasecausingvariantbasedonaselectsetofrecentexamplesinwhichhumanmutationsareinvestigatedeminvivo/emusinganimalmodels.Collectively,thesetopicswillprovideapipelinefortheuseofanimalmodelsinunderstandinghumancraniofacialdevelopmentanddiseaseforclinicalgeneticistandbasicresearchersalike./p/div