Heart Development

390 Pages·2012·8.136 MB·2-391\390

by  Benoit G. Bruneau (Eds.)

Series Editor
PaulM.Wassarman
DepartmentofDevelopmentalandRegenerativeBiology
MountSinaiSchoolofMedicine
NewYork,NY10029-6574
USA
OlivierPourquie´
InstitutdeGe´ne´tiqueetdeBiologie
CellulaireetMole´culaire(IGBMC)
InsermU964,CNRS(UMR7104)
Universite´deStrasbourg
Illkirch,France
Editorial Board
BlancheCapel
DukeUniversityMedicalCenter
Durham,NC,USA
B.DenisDuboule
DepartmentofZoologyandAnimalBiology
NCCR‘FrontiersinGenetics’
Geneva,Switzerland
AnneEphrussi
EuropeanMolecularBiologyLaboratory
Heidelberg,Germany
JanetHeasman
CincinnatiChildren’sHospitalMedicalCenter
DepartmentofPediatrics
Cincinnati,OH,USA
JulianLewis
VertebrateDevelopmentLaboratory
CancerResearchUKLondonResearchInstitute
LondonWC2A3PX,UK
YoshikiSasai
DirectoroftheNeurogenesisandOrganogenesisGroup
RIKENCenterforDevelopmentalBiology
Chuo,Japan
PhilippeSoriano
DepartmentofDevelopmentalRegenerativeBiology
MountSinaiMedicalSchool
NewYork,USA
CliffTabin
HarvardMedicalSchool
DepartmentofGenetics
Boston,MA,USA
Founding Editors
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C
ONTRIBUTORS
PhilBarnett
Department of Anatomy, Embryology and Physiology, Heart Failure Research
Center, Academic Medical Center, University of Amsterdam, Amsterdam,
TheNetherlands
BrianL.Black
Cardiovascular Research Institute and Department of Biochemistry and
Biophysics,UniversityofCalifornia,SanFrancisco,California,USA
HozanaAndradeCastillo
BrazilianNationalLaboratoryforBiosciences,BrazilianAssociationforSynchrotron
Light Technology, Rua GiuseppeMa´ximo Scolfaro, Campinas, Sa˜o Paulo,Brazil
Wen-YeeChoi
DepartmentofCellBiology,HowardHughesMedicalInstitute,DukeUniversity
MedicalCenter,Durham,NorthCarolina,USA
LionelChristiaen
CenterforDevelopmentalGenetics,DepartmentofBiology,NewYorkUniver-
sity,NewYork,USA
VincentChristoffels
Department of Anatomy, Embryology and Physiology, Heart Failure Research
Center, Academic Medical Center, University of Amsterdam, Amsterdam,
TheNetherlands
MalouvandenBoogaard
Department of Anatomy, Embryology and Physiology, Heart Failure Research
Center, Academic Medical Center, University of Amsterdam, Amsterdam,
TheNetherlands
Ramo´nA.Espinoza-Lewis
CardiovascularResearchDivision,DepartmentofCardiology,Children’sHospital
Boston,HarvardMedicalSchool,Boston,Massachusetts,USA
AibinHe
HarvardStemCellInstitute,HarvardUniversity,Cambridge,Massachusetts,USA
RobertG.Kelly
DevelopmentalBiologyInstituteofMarseilles-Luminy,Aix-MarseilleUniversite´,
CNRSUMR7288,Marseilles,France
xi
xii Contributors
JamesD.Kotick
MD Program, Leonard M. Miller School of Medicine, University of Miami,
Miami,Florida,USA
JoyLincoln
Center for Cardiovascular and Pulmonary Research, The Research Institute at
Nationwide Children’s Hospital, Department of Pediatrics, The Ohio State
University,Columbus,Ohio,USA
DavidJ.McCulley
CardiovascularResearchInstituteandDepartment of BiochemistryandBiophys-
ics,UniversityofCalifornia,SanFrancisco,California,USA
KennethD.Poss
DepartmentofCellBiology,HowardHughesMedicalInstitute,DukeUniversity
MedicalCenter,Durham,NorthCarolina,USA
WilliamT.Pu
DepartmentofCardiology,Children’sHospitalBoston,Boston,andHarvardStem
CellInstitute,HarvardUniversity,Cambridge,Massachusetts,USA
PaulR.Riley
DepartmentofPhysiology,AnatomyandGenetics,UniversityofOxford,Oxford,
OX13PT,UnitedKingdom
MichaelSchubert
Institut de Ge´nomique Fonctionnelle de Lyon (UCBL, CNRS UMR 5242,
ENSL, INRA 1288), Ecole Normale Supe´rieure de Lyon, 69364 Lyon
Cedex07,France
IanC.Scott
PrograminDevelopmentalandStemCellBiology,TheHospitalforSickChildren,
andDepartmentofMolecularGenetics,UniversityofToronto,Toronto,Ontario,
Canada
TiagoJose´ PascoalSobreira
Brazilian National Laboratory for Biosciences, Brazilian Association for Synchro-
tron Light Technology, Rua Giuseppe Ma´ximo Scolfaro, Campinas, Sa˜o Paulo,
Brazil
HenriqueMarquesSouza
Department of Histology and Embryology, Institute of Biology, University of
Campinas(UNICAMP),Campinas,Sa˜oPaulo,Brazil
AlbertoStolfi
Department of Histology and Embryology, Institute of Biology, University of
Campinas(UNICAMP),Campinas,Sa˜oPaulo,Brazil
Contributors xiii
GeTao
MolecularCellandDevelopmentalBiologyGraduateProgram,LeonardM.Miller
SchoolofMedicine,UniversityofMiami,Miami,Florida,USA
TheadoraTolkin
CenterforDevelopmentalGenetics,DepartmentofBiology,NewYorkUniver-
sity,NewYork,USA
SylviaSuraTrueba
Brazilian National Laboratory for Biosciences, Brazilian Association for Synchro-
tron Light Technology, Rua Giuseppe Ma´ximo Scolfaro, Campinas, Sa˜o Paulo,
Brazil
Da-ZhiWang
CardiovascularResearchDivision,DepartmentofCardiology,Children’sHospital
Boston,HarvardMedicalSchool,Boston,Massachusetts,USA
Jose´ Xavier-Neto
Brazilian National Laboratory for Biosciences, Brazilian Association for Synchro-
tron Light Technology, Rua Giuseppe Ma´ximo Scolfaro, Campinas, Sa˜o Paulo,
Brazil
PingzhuZhou
Department of Cardiology, Children’s Hospital Boston, Boston, Massachusetts,
USA
P
REFACE
The development of the embryonic heart is a fascinating process that
incorporates myriad molecular and morphogenetic events. These precisely
assemble multiple different cell types into a functional beating heart. The
first heart beat, early in development, is the most evident sign of life and is
essential for embryonic life. The importance of the precise assembly of the
embryonicheartisevidentinthehighincidenceofcongenitalheartdefects,
which affect several thousand children each year. The past 10 years have
seenarenaissanceinthisfieldofresearch,andinthisissueofCurrentTopics
in Developmental Biology, important advances in our understanding of the
development of the heart are reviewed.
In Chapter 1, Scott discusses the early decisions that define the initial
cardiac lineages and their differentiation, including the transcriptional cues
essential for defining the cardiac cell. Kelly follows in Chapter 2 with a
comprehensivelook atthelineages that contributetothedeveloping heart
andhowtheseareregulatedduringcardiacmorphogenesis.Theconceptof
heartfieldshasbeenattheforefrontinthepastdecade,butthisconcepthas
beencontroversial.Xavier-Netoandcolleaguescarefullyexaminetheliter-
ature and offer a different perspective on the issue in Chapter 3. The
vertebrate heart has been the focus of most studies on heart development,
and yet important insights into fundamental aspects of cardiogenesis have
been obtained from the chordate, Ciona intestinalis, which are reviewed in
Chapter 4 by Tolkin and Christiaen.
In subsequent chapters, the regulation of cardiac morphogenesis is
explored. Puandcolleagues review thevery important Gata4transcription
factor, and its impact on heart development and disease in Chapter 5.
Christoffels and colleagues in Chapter 6 tackle the concepts of transcrip-
tional regulation of localized gene expression, which is the main driving
force for precise cardiac morphogenesis, as well as the root of congenital
heartdefects.Animportantaspectofheartdevelopmentistheformationof
thevalvesthatensuredirectionalbloodflowfromonechambertothenext.
Lincolnandcolleagues inChapter7reviewrecent workon understanding
valve development and how this aspect of heart development is deeply
relevanttohumandisease.Anotherimportantcomponentoftheheartisthe
epicardium, a layer of cells that lines the outside of the heart and provides
important signals for cardiac growth. In Chapter 8, Riley reviews the
current knowledge on epicardial biology, including its potential role in
mammalian cardiac regeneration.
xv
xvi Preface
Congenital heart defects are thought to arise largely from mutations in
genesencodingfactorsimportantfor variousaspectsof heartdevelopment.
McCulley and Black in Chapter 9 review the genetics of congenital heart
disease, providing an extensive and thorough insight into the established
andpotentialgeneticabnormalitiesthatresultinabnormalheartformation.
Protein-codinggeneshavebeentheprimaryfocusofstudiesonembry-
onic development, including that of the heart. In the past several years, an
exciting discovery has been the involvement of small noncoding RNAs
knownasmicroRNAs,infine-tuningimportantaspectsofcardiacorgano-
genesis. Espinoza-Lewis and Wang review the now-extensive body of
literatureontheimportanceandbroadimpactofmicroRNA-basedregula-
tion of cardiovascular development in Chapter 10.
Finally, the past decade has seen progress on one of the most unantici-
patedandexcitingfields:vertebratecardiacregeneration.Initiallyexplored
in fish and newts, studies of cardiac regeneration have extended to mam-
malian hearts, bringing hope that damaged hearts could be endogenously
repaired. In Chapter 11, Choi and Poss review progress in understanding
the biology of cardiac regeneration.
Together, these reviews synthesize the most recent and exciting con-
cepts in heart development. The past 10 years have seen extraordinary
conceptualandtechnicaladvancesthathaverevolutionizedourunderstand-
ingofthemorphogenesisoftheheartand,mostimpressively,theimmedi-
aterelevancetohumandiseasehasrisentotheforefrontfromthisresearch.
I hope that the readers of this volume will be captivated and inspired by
these beautifully written chapters.
BENOIT G. BRUNEAU
C H A P T E R O N E
Life Before Nkx2.5: Cardiovascular
Progenitor Cells: Embryonic Origins
and Development
Ian C. Scott*,†
Contents
1. Introduction 2
2. EarlyHeartDevelopment:IsItasSimpleasLocation,
Location,Location? 3
3. CPCs:TheBuildingBlocksoftheHeart 5
4. CPCDetermination:TheQuestfor“CardioD” 6
5. SignalingPathwaysandCPCFate 14
6. AMovingStory:EarlyCPCMigrationandFate 17
7. ChangingtheProgram:CPCRelationshiptoReprogramming
andTransdifferentiation 18
8. Conclusions:FutureQuestionsandPossibleApplications 21
Acknowledgments 22
References 23
Abstract
Developmentoftheheart,likethatofotherorgans,requiresthespecificationof
progenitorcellpopulationsthatwillultimatelyformthedifferentiatedcelltypes
of the functional organ. A relatively recent and exciting advance in cardiac
researchhasbeentheidentificationofcardiovascularprogenitorcells(CPCs),
whichhavethepotentialtoformthemajorcelltypesoftheheart(cardiomyo-
cytes, smooth muscle, and endothelium/endocardium). This suggests that a
common progenitor is responsible for much of heart development and has
spurredgreatinterestinuseofCPC-likecellsforcardiacrepair.Inthisreview,
CPCdevelopmentisdiscussed,withafocusonearlyeventspriortotheinitia-
tionofcardiacgeneexpression.Inparticular,IdiscussevidencethatCPCfateis
established during gastrulation, well before a time when heart development
has typically been studied. Pathways regulating CPC specification are
* PrograminDevelopmentalandStemCellBiology,TheHospitalforSickChildren,Toronto,Ontario,Canada
{ DepartmentofMolecularGenetics,UniversityofToronto,Toronto,Ontario,Canada
CurrentTopicsinDevelopmentalBiology,Volume100 #2012ElsevierInc.
ISSN0070-2153,DOI:10.1016/B978-0-12-387786-4.00001-4 Allrightsreserved.
1
2 IanC.Scott
examined.TherelationshipbetweenCPCspecificationandmigrationisfurther
discussed. Finally, how CPCs may be related to efforts to promote cardiac
developmentbyapproachesincludingreprogrammingisdiscussed.
1. Introduction
Developmentandgrowthofthehearthasbeenahighlyactiveareaof
research in the past few decades. Organogenesis in general requires the
specification of progenitor cell(s), their migration to the organ-forming
region, interactions and signalingwithin andbetween tissues, morphogen-
esis to form the proper organ shape, differentiation of progenitor cells to
required specialized and subspecialized cell types, and later growth and
functional maturation of the organ. Great progress has been made in
delineating the molecular and cellular processes that drive heart tube for-
mation and later cardiac morphogenesis and maturation. However, the
earliest events of heart development—when the progenitor cells that form
the heart arise—have been more difficult to examine. This has largely
stemmed from an absence of markers to characterize heart progenitors.
A relatively recent and exciting advance in cardiac research has been
the identification of cardiovascular progenitor cells (CPCs), which have
the potential to form many of the major cell types of the heart (cardio-
myocytes, endothelium/endocardium, and smooth muscle; Kattman et al.,
2006; Moretti et al., 2006; Wu et al., 2006). This suggests that a common
progenitor is responsible for much of heart development and has spurred
great interest in use of CPC-like cells for cardiac repair. Excellent reviews
in the past year have been focused on early events of heart development
(Evans et al., 2010; Lopez-Sanchez and Garcia-Martinez, 2011; Meilhac
and Buckingham, 2010; Vincent and Buckingham, 2010), and it is not
my intention in this review to revisit events covered in detail in these
works.
Inthisreview,earlyeventsofCPCdevelopmentarediscussed,priorto
the initiation of cardiac gene expression. It should be noted that the
contribution of the cardiac neural crest, clearly a key participant in heart
development (Hutson and Kirby, 2007), is not covered in this chapter. In
particular,Ifocusonevidencefromanimalandinvitrostemcellmodelsthat
CPC fate is established during gastrulation, well before a time when heart
development has typically been studied. The relationship between embry-
onic CPCs and efforts to promote cardiac development by approaches
including reprogramming will then be examined. Finally, what I see as
futureoutstandingquestionsinCPCbiologyandtherapeuticpotentialwill
be discussed.
OriginsandDevelopmentofHeartProgenitors 3
2. Early Heart Development: Is It as Simple as
Location, Location, Location?
Wheredoestheheartcomefrom?Fordecades,ithasbeenknownthat
cardiomyocytes arise from bilateral populations of anterior lateral plate
mesoderm (ALPM; Dehaan, 1963; Stalsberg and DeHaan, 1969). These
elegantchickstudiesshowedthatthesebilateralpopulationslaterfuseatthe
midline to form the linear heart tube. Explant of tissues to this precardiac
mesoderm area can induce cardiac fate (Schultheiss et al., 1995; Tam et al.,
1997).Inthemorerecent“molecularbiologyera,”workfromanumberof
groups has shown that this region of the ALPM is privileged for cardiac
mesodermdevelopment.Thisisachievedthroughabalanceofsignals,both
stimulatoryandinhibitoryforcardiacdifferentiation.ProcardiacBMPsand
FGFsaresecretedfromtheadjacentlateralendodermandectoderm,which
promote both early myocardial fate and further differentiation of cardio-
myocytes (Barron et al., 2000; Reifers et al., 2000; Schultheiss et al., 1997;
Shi et al., 2000). In contrast, the neurectoderm secretes WNTs, which
inhibits cardiac mesoderm formation at the ALPM stage. The secretion of
WNT inhibitors in the anterior portion of the embryo further restricts
cardiac fate (Marvin et al., 2001; Schneider and Mercola, 2001). The
integration of these signals results in cardiac mesoderm being present in
specific bilateral positions in a defined anterior region of the embryo.
Indeed, perturbation of these gradients of signals can result in ectopic or
an absence of myocardial differentiation.
Amajoradvanceinthefieldofearlycardiacfatearosefromstudyofthe
Drosophila melanogaster (fruit fly) tinman mutant, which lacks a dorsal vessel
(theflyheart equivalent,essentiallyabeatingtube)(Bodmer,1993).Clon-
ing of the vertebrate tinman homologue, which encodes the NK-class
homeodomain transcription factor Nkx2.5 (also referred to as Csx) fol-
lowed. Importantly, analysis of Nkx2.5 expression revealed that it is
initiated in two bilateral stripes of the ALPM, mirroring in general the
precardiac mesoderm described by embryological studies (Chen and
Fishman,1996;Schultheissetal.,1995;Tonissenetal.,1994).Itisimportant
tonotethattheNkx2.5-positiveALPMpopulationdoesnotrepresentALL
ofthefuturemyocardium.AtALPMstagesinmultiplevertebratespecies,a
large portion of the future second-heart field myocardium is largely
devoid of Nkx2.5 expression (Brade et al., 2007; Cai et al., 2003; Hami
etal.,2011;YutzeyandKirby,2002).Conversely,themajorityof,butnot
all Nkx2.5-positive cells will contribute to the heart (Goldstein and
Fishman, 1998; Raffin et al., 2000; Redkar et al., 2001). In the fruit fly,
dorsalvesselformationandtinmanexpressionaredependentonFGF,BMP
(dpp in flies), and WNT signaling (Beiman et al., 1996; Frasch, 1995;