Table Of ContentCURRENT TOPICS IN
DEVELOPMENTAL BIOLOGY
“Ameeting-groundforcriticalreviewanddiscussionofdevelopmentalprocesses”
A.A.MosconaandAlbertoMonroy(Volume1,1966)
SERIES EDITOR
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Department ofDevelopmental andRegenerative Biology
IcahnSchool ofMedicine atMount Sinai
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CONTRIBUTORS
AnnitaAchilleos
StowersInstituteforMedicalResearch,KansasCity,Missouri,USA
ZhengwenAn
CraniofacialDevelopmentandStemCellBiology,DentalInstitute,KingsCollegeLondon,
London,UnitedKingdom
KristinB.Artinger
DepartmentofCraniofacialBiology,UniversityofColoradoAnschutzMedicalCampus,
Aurora,Colorado,USA
RebeccaBabb
CraniofacialDevelopmentandStemCellBiology,DentalInstitute,KingsCollegeLondon,
London,UnitedKingdom
AnamariaBalic
ResearchPrograminDevelopmentalBiology,InstituteofBiotechnology,Universityof
Helsinki,Helsinki,Finland
RyanF.Bloomquist
SchoolofBiology,PetitInstituteforBioengineeringandBioscience,GeorgiaInstituteof
Technology,Atlanta,Georgia,USA
JeffreyO.Bush
PrograminCraniofacialBiology;DepartmentofCellandTissueBiology,andInstitutefor
HumanGenetics,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,USA
YangChai
CenterforCraniofacialMolecularBiology,UniversityofSouthernCalifornia,LosAngeles,
California,USA
DavidE.Clouthier
DepartmentofCraniofacialBiology,UniversityofColoradoAnschutzMedicalCampus,
Aurora,Colorado,USA
GageCrump
EliandEdytheBroadCIRMCenterforRegenerativeMedicineandStemCellResearchat
theUniversityofSouthernCalifornia,LosAngeles,California,USA
TamarEigler
DepartmentofBiologicalRegulation,WeizmannInstituteofScience,Rehovot,Israel
JianQ.Feng
DepartmentofBiomedicalSciences,TexasA&MBaylorCollegeofDentistry,Dallas,Texas,
USA
TeresaE.Fowler
SchoolofBiology,PetitInstituteforBioengineeringandBioscience,GeorgiaInstituteof
Technology,Atlanta,Georgia,USA
xiii
xiv Contributors
ScottE.Fraser
MolecularandComputationalBiology,UniversityofSouthernCalifornia,LosAngeles,
California,USA
JenniferC.Fuchs
DepartmentofCraniofacialDevelopment&StemCellBiology,King’sCollegeLondon,
London,UnitedKingdom
AliceF.Goodwin
PrograminCraniofacialBiology,andDepartmentofOrofacialSciences,Universityof
CaliforniaSanFrancisco,SanFrancisco,California,USA
YongchaoGou
StateKeyLaboratoryofOralDiseases,DepartmentofOrthodontics,WestChina
HospitalofStomatology,SichuanUniversity,Chengdu,China,andCenterfor
CraniofacialMolecularBiology,SchoolofDentistry,UniversityofSouthernCalifornia,
LosAngeles,USA
RebeccaGreen
DepartmentofCellBiologyandAnatomy,AlbertaChildren’sHospitalResearchInstitute,
andMcCaigBoneandJointInstitute,UniversityofCalgary,Calgary,Alberta,Canada
BenediktHallgrimsson
DepartmentofCellBiologyandAnatomy,AlbertaChildren’sHospitalResearchInstitute,
andMcCaigBoneandJointInstitute,UniversityofCalgary,Calgary,Alberta,Canada
BelindaR.Hauser
MatrixandMorphogenesisSection,LaboratoryofCellandDevelopmentalBiology,
NationalInstituteofDentalandCraniofacialResearch,NationalInstitutesofHealth,
Bethesda,Maryland,USA
RobertJ.Hinton
DepartmentofBiomedicalSciences,TexasA&MBaylorCollegeofDentistry,Dallas,Texas,
USA
MatthewP.Hoffman
MatrixandMorphogenesisSection,LaboratoryofCellandDevelopmentalBiology,
NationalInstituteofDentalandCraniofacialResearch,NationalInstitutesofHealth,
Bethesda,Maryland,USA
MamoruIshii
DepartmentofBiochemistryandMolecularBiology,USCNorrisComprehensiveCancer
Center,KeckSchoolofMedicine,UniversityofSouthernCalifornia,LosAngeles,
California,USA
RulangJiang
DivisionofDevelopmentalBiology,andDivisionofPlasticSurgery,CincinnatiChildren’s
HospitalMedicalCenter,Cincinnati,Ohio,USA
JunjunJing
StateKeyLaboratoryofOralDiseases,WestChinaHospitalofStomatology,Sichuan
University,Sichuan,PRChina
Contributors xv
RebeccaKim
PrograminCraniofacialBiology,andDepartmentofOrofacialSciences,Universityof
CaliforniaSanFrancisco,SanFrancisco,California,USA
OphirD.Klein
PrograminCraniofacialBiology;DepartmentofOrofacialSciences;Departmentof
Pediatrics,andInstituteforHumanGenetics,UniversityofCaliforniaSanFrancisco,San
Francisco,California,USA
YuLan
DivisionofDevelopmentalBiology,andDivisionofPlasticSurgery,CincinnatiChildren’s
HospitalMedicalCenter,Cincinnati,Ohio,USA
RalphMarcucio
DepartmentofOrthopaedicSurgery,SanFranciscoGeneralHospital,OrthopaedicTrauma
Institute,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,USA
RobertE.Maxson
DepartmentofBiochemistryandMolecularBiology,USCNorrisComprehensiveCancer
Center,KeckSchoolofMedicine,UniversityofSouthernCalifornia,LosAngeles,
California,USA
AmyE.Merrill
DepartmentofBiochemistryandMolecularBiology,KeckSchoolofMedicine,andCenter
forCraniofacialMolecularBiology,OstrowSchoolofDentistry,UniversityofSouthern
California,LosAngeles,California,USA
InbalMichailovici
DepartmentofBiologicalRegulation,WeizmannInstituteofScience,Rehovot,Israel
WashingtonMio
DepartmentofMathematics,FloridaStateUniversity,Tallahassee,Florida,USA
LindseyMork
EliandEdytheBroadCIRMCenterforRegenerativeMedicineandStemCellResearchat
theUniversityofSouthernCalifornia,LosAngeles,California,USA
CynthiaL.Neben
DepartmentofBiochemistryandMolecularBiology,KeckSchoolofMedicine,University
ofSouthernCalifornia,LosAngeles,California,USA
CarolinaParada
CenterforCraniofacialMolecularBiology,UniversityofSouthernCalifornia,LosAngeles,
California,USA
ChristopherJ.Percival
DepartmentofCellBiologyandAnatomy,AlbertaChildren’sHospitalResearchInstitute,
andMcCaigBoneandJointInstitute,UniversityofCalgary,Calgary,Alberta,Canada
PedroA.Sanchez-Lara
DirectorofCraniofacialGenetics,Children’sHospitalLosAngeles;AssistantProfessorof
ClinicalPediatrics;AssistantProfessorofClinicalPathology,andResearchInstructorCenter
forCraniofacialMolecularBiology,HermanOstrowSchoolofDentistry,Universityof
SouthernCalifornia,LosAngeles,California,USA
xvi Contributors
RichardA.Schneider
DepartmentofOrthopaedicSurgery,UniversityofCaliforniaatSanFrancisco,San
Francisco,California,USA
PaulT.Sharpe
CraniofacialDevelopmentandStemCellBiology,DentalInstitute,KingsCollegeLondon,
London,UnitedKingdom
JingjingSun
DepartmentofBiochemistryandMolecularBiology,USCNorrisComprehensiveCancer
Center,KeckSchoolofMedicine,UniversityofSouthernCalifornia,LosAngeles,
California,USA
AndreL.P.Tavares
DepartmentofCraniofacialBiology,UniversityofColoradoAnschutzMedicalCampus,
Aurora,Colorado,USA
IrmaThesleff
ResearchPrograminDevelopmentalBiology,InstituteofBiotechnology,Universityof
Helsinki,Helsinki,Finland
Man-ChunTing
DepartmentofBiochemistryandMolecularBiology,USCNorrisComprehensiveCancer
Center,KeckSchoolofMedicine,UniversityofSouthernCalifornia,LosAngeles,
California,USA
J.ToddStreelman
SchoolofBiology,PetitInstituteforBioengineeringandBioscience,GeorgiaInstituteof
Technology,Atlanta,Georgia,USA
PaulA.Trainor
StowersInstituteforMedicalResearch,KansasCity,Missouri,andDepartmentofAnatomy
&CellBiology,UniversityofKansasMedicalCenter,KansasCity,Kansas,USA
LeA.Trinh
MolecularandComputationalBiology,UniversityofSouthernCalifornia,LosAngeles,
California,USA
AbigailS.Tucker
DepartmentofCraniofacialDevelopment&StemCellBiology,King’sCollegeLondon,
London,UnitedKingdom
EldadTzahor
DepartmentofBiologicalRegulation,WeizmannInstituteofScience,Rehovot,Israel
AnaAngelovaVolponi
CraniofacialDevelopmentandStemCellBiology,DentalInstitute,KingsCollegeLondon,
London,UnitedKingdom
JianXu
CenterforCraniofacialMolecularBiology,SchoolofDentistry,UniversityofSouthern
California,LosAngeles,USA
Contributors xvii
JingyueXu
DivisionofDevelopmentalBiology,CincinnatiChildren’sHospitalMedicalCenter,
Cincinnati,Ohio,USA
NathanM.Young
DepartmentofOrthopaedicSurgery,SanFranciscoGeneralHospital,OrthopaedicTrauma
Institute,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,USA
TianYu
CraniofacialDevelopmentandStemCellBiology,DentalInstitute,KingsCollegeLondon,
London,UnitedKingdom
TingweiZhang
CenterforCraniofacialMolecularBiology,SchoolofDentistry,UniversityofSouthern
California,LosAngeles,USA,andStateKeyLaboratoryofOralDiseases,Departmentof
Prosthodontics,WestChinaHospitalofStomatology,SichuanUniversity,Chengdu,China
PREFACE
INTRODUCTION TO CRANIOFACIAL DEVELOPMENT
Thedevelopmentofthecraniofacialcomplexliesatthecoreofwhatmakes
us human. Theface housesour sensory organsandthe craniumcradlesthe
brain.Anyaberrationsincraniofacialdevelopmentcanthereforejeopardize
fundamentalprocessesthatallowustosurvive,thrive,andenjoyourworld:
our senses of sight, hearing, smell, and taste; our ability to eat, drink, and
breathe; our intellectual capacity. Moreover, the uniquely individual face
representsoneofthemostimportantandsalientpartsoftheidentitywepre-
senttoourpeers.Forallofthesereasons,craniofacialdevelopmenthaslong
been a source of fascination to scientists.
Beginninginthemid-twentiethcentury,itbecameclearthattheunique
challenges of understandingcraniofacial biology arebestsuitedto aninter-
disciplinaryteamapproach,dueinlargeparttoluminariesofthefieldsuchas
HansSpemann,HildeMangold,andSamuelPruzansky.Thecontributions
to the present volume continue this tradition, building on scientific and
technological advances in developmental biology, molecular genetics, and
medicine to bring a multitude of perspectives to bear on issues pertaining
to craniofacial development. The authors hail from the fields of develop-
mentalpatterning,cellandmolecularbiology,stemcellbiology,evolution-
ary biology, clinical genetics, and everything in between. As a result, this
bookprovidesacomprehensiveoverviewofthecurrentstatusofourunder-
standing of craniofacial development.
Thisbookisorganizedintothreesections.Thefirstsectiondiscussesaspects
ofcraniofacialmorphogenesisandregenerationonmultiplescales,fromcellsto
tissues to organs. Many of our unique organs are housed in the craniofacial
region,yettheregulatorymechanismsofcell–cellinteractions,tissuedevelop-
ment,and organogenesis share common features withthosethatcontrolthe
development of the rest of the body. The major families of growth factors
(BMP/TGF-β,FGF,Wnt,andHh)areallinvolvedintheregulationofcra-
niofacial development. The signaling specificity of these growth factors lies
withthecells,whichhaveuniquetranscriptionfactorsandothergeneticand
epigeneticregulatorsthatcollectivelydeterminetheoutcomeofgrowthfactor
signalingduringcraniofacialmorphogenesis.Thechaptersinthissectionoffer
evolutionary and embryonic perspectives on the regulation of the facial
xix
xx Preface
muscles,mandible,tongue,palate,temporomandibularjoint,cranialsutures,
tooth,andeardevelopment.Thesestudiesprovideanin-depthoverviewofcell
fatedeterminationandhowcontinuedtissue–tissueinteractionscontrolcranio-
facialdevelopmentandregeneration.
The second section focuses on craniofacial patterning and signaling
mechanisms. The principal goal of developmental biology is to understand
how tissues are induced and patterned to generate different organs at the
proper location and time. Evidence suggests that signals from the anterior
visceral endoderm, anterior neural ridge, and mesoderm are required for
thedevelopmentofcraniofacialstructures.Theformationofthevertebrate
“New Head” depends upon the presence of cranial neural crest cells and
additionalsensoryplacodes.Multiplemoleculeshavebeenidentifiedascru-
cialregulatorsfortissue–tissueinteractionsduringcraniofacialdevelopment.
Usingfish,chick,mouse,andotheranimalmodels,thechaptersinthissec-
tionprovideasummaryofourcurrentunderstandingofhowearlycranio-
facial patterning is established and how signaling networks control
craniofacial morphogenesis.
The third section of the volume is centered around disease models,
human genetics, genomics,andnew approaches in dynamicimaging. Ani-
mal models have clearly played an important role in our understanding of
normalandabnormalcraniofacialdevelopment.Yetdespitethevastamount
of knowledge that we have gained from animal studies, shortcomings
remain:for example,apparently onlyonethird of mousemutations associ-
ated with craniofacial defects have been linked to mutations of the
orthologous human genes with similar dysmorphologies. It is not known
what defects might arise from mutations of the other two thirds of these
genes, as some of these mutations result in early embryonic lethality. It is
of paramount importance that there are constant interactions between
researchersinvolvedinhumanandanimalstudies,asthiswillensurearapid
translationoffundamentaldiscoveriesintotreatmentandpreventionofcra-
niofacial malformations in humans. Craniofacial malformations represent
complexmultifactorialdiseases,amplifiedorattenuatedbygene–geneinter-
actions, gene–environmental interactions, environmental influences, and
mechanicalfactors.Therapidtechnologicaladvancementanddecreasedcost
ofsequencingthehumangenomewillundoubtedlyfacilitatethediscovery
of genetic mutations involved in human craniofacial malformations. Fur-
thermore,thisnewinformationwillfacilitatethedesignandimplementation
ofprecisionmedicine.Finally,theimprovedspatialandtemporalresolution
Preface xxi
ofdynamicandliveimagingwillalsoelevateourstudyofcraniofacialdevel-
opment to the next level of insight and excellence.
It has been an extremely rewarding experience working with so many
talented and accomplished scientists and clinicians in putting together this
book.Iwouldliketoexpressmytremendousgratitudetothemforthetime
andefforttheydevotedtothisproject.Itismyhopethatourauthors’diverse
perspectiveswillprovideawell-roundedviewofthecurrentstateofaffairs
in craniofacial development and a springboard for further advances in
the field.
YANG CHAI, DDS, PhD Professor
George and MaryLou Boone Chair in Craniofacial Biology
University of Southern California
