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DEVELOPMENT%20OF%20HEART

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Dr. Shreetal Rajan Nair TRANSCRIPTIONAL REGULATORS ABNORMALITIES OF DEVELOPMENT From Fertilization to Primitive Heart Tube Abnormal development at this stage of ... – PowerPoint PPT presentation

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Title: DEVELOPMENT%20OF%20HEART


1
DEVELOPMENT OF HEART
  • Dr. Shreetal Rajan Nair

2
Introduction
  • Human heart starts to develop during the 3rd week
    of embryonic life. Till then the needs of the
    embryo are met through simple diffusion of blood
    between the germ layers.
  • Cardiogenesis in humans is associated with
    complex morphogenetic events

3
Area of discussion
  • Anatomic
  • Molecular
  • Clinical aspects

4
Cardiac development
  • Early development
  • Formation of the trilaminar embryo
  • Origin of cardiogenic cells
  • Formation of bilateral heart fields
  • Formation of the heart tube
  • Folding of the heart tube
  • Looping of the heart tube
  • Cardiac developmental abnormalities

5
The Beginnings(fetal landmarks)
  • Day 0 Fertilisation forming zygote initiating
    embryogenesis
  • 2 cell stage 4 cell stage morula
  • Week 1 implantation ( as a blastocyst)
  • Week 2 bilaminar stage (epiblast,hypoblast)
  • Week 3 gastrulation primitive streak,notochord
    and neural plate begin to form
  • Week 4 heart begins to form.

6
Week 1 beginning of development
  • Day 1-Fertilisation and formation of zygote
  • Day 2 2 cell blastula
  • Day 3 4 cell blastula
  • Day 4 morula ( 32 cell stage)
  • Day 5 blastocyst ( inner cell mass of
    embryoblast and outer cell mass called
    trophoblast)
  • Day 6 - implantation

7
1st week
8
1st week
9
1st week
10
BLASTOCYST FORMATION
11
WEEK 2 FORMATION OF BILAMINAR EMBRYO
12
Week 3
13
Week 3
14
Week 3
15
SUMMARY- Early development
  • Rule of 2s for 2nd week
  • 2 germ layers (bilaminar disk) epiblast,
    hypoblast.
  • 2 cavities amniotic cavity,yolk sac
  • Rule of 3s for 3rd week
  • 3 germ layers ( gastrula)
    ectoderm,mesoderm and endoderm

16
  • Cardiac Embryogenesis

17
Sequence of events
  • Occurs towards the end of the 3rd week
  • Day I8 - cardiac precursor cells seen in the
    form of blood islands
  • Day 20 - first intraembryonic blood vessels
    seen
  • Day 21- Folding, heart tube formation,looping
  • Day 22 heart starts to beat, ebb and flow
    initially
  • Day 28 embryonic circulation established

18
Cardiac development
  • Early development
  • Formation of trilaminar embryo
  • Origin of cardiogenic cells
  • Formation of bilateral heart fields
  • Formation of the heart tube
  • Folding of the heart tube
  • Looping of the heart tube
  • Cardiac developmental abnormalities

19
  •  The developing blood vessels and heart tube can
    be seen in an embryo at approximately 18 days .
  • When looking down at this early embryo you can
    see multiple blood islands dispersed throughout
    the embryo.

20
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21
Origin of cardiac precursor cells
  • The heart primordium arises predominantly from
    the mesoderm in the cardiogenic region of the
    trilaminar embryo.

22
Cardiac precursor cells
  • First heart field (FHF)
  • Second heart field (SHF)
  • Proepicardium
  • Cardiac neural crest cells

23
Cardiac precursor cells
  • FHF
  • SHF
  • CNC
  • Proepicardium

24
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25
Cardiac development
  • Early development
  • Origin of cardiogenic cells
  • Formation of bilateral heart fields
  • Formation of the heart tubes
  • Folding of the heart tube
  • Looping of the heart tube
  • Cardiac development abnormalities

26
The concept of heart fields
  • Two distinct mesodermal heart fields that share a
    common origin appear to contribute cells to the
    developing heart in a temporally and spatially
    specific manner.
  • Using special technologies to mark progenitor
    cells two heart fields (the primary and
    secondary) have been characterised.

27
  • The heart tube derived from the primary heart
    field may predominantly provide a scaffold that
    enables a second population of cells to migrate
    and expand into cardiac chambers .
  • These additional cells arise from an area often
    referred to as the secondary heart field (SHF),
    or anterior heart field, based on its location
    anterior and medial to the crescent-shaped
    primary heart field

28
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29
HEART FIELDS
  • SHF cells cross the pharyngeal mesoderm into the
    anterior and posterior portions, contributing to
    the formation of the outflow tract, future right
    ventricle, and atria

30
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31
Pathophysiology
32
Cardiac development
  • Early development
  • Origin of cardiogenic cells
  • Formation of bilateral heart fields
  • Formation of the heart tube
  • Folding of the heart tube
  • Looping of the heart tube
  • Cardiac developmental abnormalities

33
  • The flat germ disk transforms into a tubular
  • structure during the fourth week of
    development
  • This is achieved through a process of
    differential growth causing the embryo to fold in
    two different dimensions

34
Formation of the endocardial tube
  • The heart initially forms from two tubes located
    bilaterally (on either side) of the trilaminar
    embryo in the cranial (head)

35
  • This primitive, bilateral heart tubes each
    contains an inner layer of endocardium, a middle
    layer of cardiac jelly, and an outer layer of
    myocardium region

36
Folding of the embryo
  • 1. Craniocaudal axis due to the more rapid growth
    of the neural tube forming the brain at its
    cephalic end. Growth in this direction will cause
    the embryo to become convex shaped.
  • 2.Lateral folding, causing the two lateral edges
    of the germ disk to fold forming a tube-like
    structure

37
THE CARDIOGENIC AREA
38
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39
Formation of the endocardial tube
  • The primitive heart tubes then fuse in the
    ventral midline to form the linear or straight
    heart tube in a cranial to caudal direction

40
  • Simultaneously the heart tube shows a series of
    dilatations.
  • From cranial to caudal these are
  • Bulbous cordis
  • Ventricle
  • Atrium
  • Sinus venosus

41
  • The arterial trunk will divide to separate the
    pulmonary and systemic supply.
  • The bulbus and the ventricle will later
    differentiate into the right and left ventricle

42
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43
Arterial end of the heart
  • Bulbus cordis represents the arterial end of
    heart. It consists of
  • proximal part called the conus
  • a distal part called truncus arteriosus.
  • The truncus continues distally with the aortic
    sac.

44
VENOUS END OF THE HEART TUBE
  • The sinus venosus represents the venous end of
    the heart. One vitelline vein from the yolksac
    one umbilical vein from the placenta and one
    common cardinal vein from the bodywall ,joins
    each horn of the sinus venosus.

45
  • After the formation of the head fold, this tube
    lies dorsal to the pericardial cavity and ventral
    to the foregut.
  • Splanchnopleuric mesoderm lining the dorsal side
    of the pericardial cavity proliferates to forma
    thick layer called the myoepicardial mantle.

46
  • When the invagination is complete, the
    myoepicardial mantle completely surrounds the
    heart tube
  • It gives rise to the cardiac muscle (MYOCARDIUM)
    and also to the visceral layer of the pericardium
    (EPICARDIUM)

47
EXTERIOR OF THE HEART
  • Heart tube is suspended from the dorsal wall of
    the pericardial cavity by 2 layers of pericardium
    that constitutes dorsal mesocardium

48
  • A hole forms in the dorsal mesocardium which
    increases in size.
  • Gradually Mesocardium disappears and the heart
    tube lies free within the pericardial cavity
  • Mesocardium disappears to form the transverse
    sinus of the pericardium

49
Cardiac development
  • Early development
  • Origin of cardiogenic cells
  • Formation of bilateral heart fields
  • Formation of the heart tube
  • Folding of the heart tube
  • Looping of the heart tube
  • Cardiac developmental abnormalities

50
Cardiac looping
  • Looping of the heart tube allows the straight
    heart tube to form a more complex structure
    reminiscent of the adult heart. Most cardiac
    looping occurs during the fourth week and
    completes during the fifth week of development

51
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52
  • The linear heart tube develops differential
    growth of the heart tube in comparison with the
    foregut
  • The direction of cardiac looping is determined by
    an asymmetric signalling system which affects
    the position of both thoracic and abdominal
    contents

53
  • In all vertebrates, there is differential growth
    within the heart tube itself resulting in
    posterior, leftward, slower growth and anterior,
    rightward, faster growth resulting in rightward
    looping. This positioning results in the future
    right ventricle taking an anterior and rightward
    location with reference to the future left
    ventricle

54
  • Further disproportionate growth of the heart tube
    in comparison to the foregut results in bending
    of the heart tube at the inflow as well as within
    the ventricular segment eventually positioning
    the inflow and future left ventricular segments
    posteriorly and to the left, with the future
    right ventricle and outflow segments anteriorly
    and to the right

55
  • The straight heart tube begins to elongate with
    simultaneous growth in the bulbus cordis and
    primitive ventricle
  • This forces the heart to bend ventrally and
    rotate to the right, forming a C-shaped loop with
    convex side situated on the right.
  • The ventricular bend moves caudally and the
    distance between the outflow and inflow tracts
    diminishes.
  • The atrial and outflow poles converge and
    myocardial cells are added, forming the truncus
    arteriosus

56
  • Hence an S-shape is formed with the first bend of
    the 'S' being the large ventricular bend while
    the bend at the junction of the atrium and sinus
    venosus forms the second 'S' bend

57
The cardiac tube grows at a greater longitudinal
rate then the rest of the embryo, causing it to
fold. As it does this it falls to the right.
This is known as d-looping. It may fall to the
left in an l-loop this will lead to a malformed
heart. Below are chick embryo dissections
showing the two types of loop.
normal d-loop l-loop
58
  • The fold of the loop is principally at the
    junction of bulbus cordis and ventricle. Note in
    panel C that the two end up side by side.
  • The left ventricle will develop from the
    ventricle, and the right ventricle will develop
    from the bulbus cordis. (And an l-loop will
  • result in ventricular inversion with the left
    ventricle on the right.
  • Note also that the arterial trunk is above the
    developing right ventricle.

59
Time line of cardiogenesis
60
MOLECULAR ASPECTS IN CARDIOGENESIS
  • Transcriptional regulators
  • Epigenetic regulation by microRNAs (miRNA)

61
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62
ROLE OF RETINOIC ACID
  • HENSONS NODE which contains retinoic acid,
    serves as an embryonic organizer that confers
    information required to direct the ultimate fate
    of mesodermal cells during early embryogenesis.
  • Exogenous retinoic acid is extremely teratogenic
    at that stage
  • Greatest effect is on the arterial pole.

63
Cardiac development
  • Early development
  • Origin of cardiogenic cells
  • Formation of bilateral heart fields
  • Formation of the heart tubes
  • Folding of the heart tube
  • Looping of the heart tube
  • Cardiac development abnormalities

64
Pathophysiology
  • Abnormal left-right signalling
  • Looping defects
  • Defects due to abnormal migration of cells of
    primary and secondary heart fields and of cardiac
    neural crest

65
One disease several mechanisms several genes
66
TRANSCRIPTIONAL REGULATORS
67
ABNORMALITIES OF DEVELOPMENT
  • From Fertilization to Primitive Heart Tube
  • Abnormal development at this stage of
  • embryogenesis almost always results in
    embryonic death because of the critical nature
    of the early circulation to the further growth
    and development of the embryo and fetus.

68
DEFECTIVE EXPRESSION OF TRANSCRIPTIONAL FACTORS
  • Absence of Hand2 (dHAND) results in
  • RV HYPOPLASIA or ABSENT RV

69
Abnormalities due to abnormal left-right
signalling and dorso ventral polarity
  • HETEROTAXY SYNDROMES
  • DORV
  • DILV

70
Pathophysiology
71
  • In humans, mirror-image reversal of left-right
  • asymmetry is often associated with normal
    organ development ( simple dextrocardia or situs
    inversus totalis) but discordance of thoracic and
    visceral asymmetry universally results in
    defective organogenesis, the most common being
    heterotaxy syndrome.

72
HETEROTAXY SYNDROMES
73
Abnormalities of looping
  • Ventricular Inversion with Transposition of the
    Great Arteries

74
  • There is currently considerable research in
    animate models on the genes known to control
    left-right development. Similarly, congenitally
    corrected transposition of the great arteries is
    thought to result from both an abnormality of
    looping and of outflow tract development.
  • Many other complex abnormalities involving both
    ventricles and outflow tract are thought to have
    at least some abnormality in the looping process.

75
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76
Defective migration of cells
  • HYPOPLASIA OF RVOT/MPA - TOF
  • ABSENCE OF RVOT/MPA- TA
  • ABSENCE OF AORTO-PULMONARY SEPTUM TA
  • MALALINGMENT OF AORTA AND LV ABNORMAL WEDGING
    -TOF
  • ABNORMAL MYOCARDIAL TRABECULATION- LV/RV NON
    COMPACTION

77
DEVELOPMENT ABNORMALITIES
78
BIBLIOGRAPHY
  • Braunwalds Heart Disease 9th edition
  • Hursts THE HEART 13th edition, chapter 9.
  • Moss and Adams Heart Disease , 7th edition
  • Harrisons Text Book of Internal Medicine,18th
    edition
  • Embryology and Congenital Heart Disease,Paolo
    Angelini, MD
  • Cardiac Chamber FormationDevelopment, Genes,
    and Evolution
  • ANTOON F. M. MOORMAN AND VINCENT M.
    CHRISTOFFELS 83 12231267, 2003
    10.1152/physrev.00006.2003
  • 7. Regulation of myocardial gene
    expression during heart development
  • Diego Franco ,Jorge Domínguez , María
    del Pilar de Castro , Amelia Aránega
  • Rev Esp Cardiol. 200255167-84. - Vol.
    55 Núm.02
  • Molecular embryology for an understanding of
    congenital heart diseases Hiroyuk i Yamagishi
    et al. Anat Sci Int (2009) 848894 Received
    27 May 2008 / Accepted 16 June 2008 /
    Published online 7 April 2009 Japanese
    Association of Anatomists 2009
  • 9. Cardiovascular Embryology R. Abdulla,G.
    A. Blew,M.J. Holterman Pediatr Cardiol
    25191200, 2004

79
Bibliography
  • 10. Wherefore heart thou? Embryonic origins of
    cardiogenic mesoderm Katherine E. Yutzey
    ,Margaret L. Kirby , Developmental Dynamics ,
    volume 223 issue 3pages 307320, March 2002

80
  • Quiz

81
Cardiac precursors develop from all except1.
FHF2. SHF3. NEURAL CREST4. PROEPICARDIUM5.NONE
82
Atria receives contributions from
  • 1 FHF
  • 2. SHF
  • 3.BOTH
  • 4.NEURAL CREST

83
BLOOD ISLANDS SEEN ON DAY
  • 1. 17
  • 2. 18
  • 3. 19
  • 4.20

84
RIGHT VENTRICLE DEVELOPS FROM1.FHF2.SHF3.CNC4
.PROEPICARDIUM
85
CORONARY VESSELS DEVELOP FROM
  • 1. FHF
  • 2.SHF
  • 3.CNC
  • 4.PROEPICARDIUM

86
  • THANK YOU
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