2009 Lecture 7

From Embryology

Early Vascular Development

Mouse embryo (19 somite) vascular distribution

Introduction

This lecture will introduction to the events in early embryonic development that relate to mesoderm and early cardiovascular development. Most texts will separate heart development from vascular development in order to simplify their descriptions of cardiovascular development, though the two are functionally and embryonically connected. Note that we will be returning later to discuss the late development of the heart and vascular changes.

The complexity of septation, cardiac outflow separation, remodelling of the peripheral vasculature, and the pre- to post-natal changes may also contribute to the relatively large proportion of birth defects associated with this system.

The molecular mechanisms regulating cardiac development are still largely unknown. Development does appear to be an independent mechanism preceding both skeletal and smooth muscle development and using different regulatory mechanisms (not MyoD or myogenin).

Lecture Objectives

Historic image of early human vascular development
  • Understanding of mesoderm development
  • Understanding of heart tube formation and early development
  • Understanding of early blood vessel and blood development
  • Brief understanding of vascular growth and regression
  • Brief understanding of vascular growth factors

Textbook References

  • Human Embryology (3rd ed.) Larson Chapter 7 p151-188 Heart, Chapter 8 p189-228 Vasculature
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Chapter 14: p304-349

Other textbooks

  • Before we Are Born (5th ed.) Moore and Persaud Chapter 12; p241-254
  • Essentials of Human Embryology Larson Chapter 7 p97-122 Heart, Chapter 8 p123-146 Vasculature
  • Human Embryology Fitzgerald and Fitzgerald Chapter 13-17: p77-111

Recent reviews

  • Yutzey KE, Kirby ML. Wherefore heart thou? Embryonic origins of cardiogenic mesoderm. Dev Dyn. 2002 Mar;223(3):307-20. Review. PMID: 11891982
  • Three-dimensional reconstruction of gene expression patterns during cardiac development. Soufan AT, Ruijter JM, van den Hoff MJ, de Boer PA, Hagoort J, Moorman AF. Physiol Genomics. 2003 May 13;13(3):187-95. Review. PMID: 12746463
  • Moorman A, Webb S, Brown NA, Lamers W, Anderson RH. Development of the heart: (1) formation of the cardiac chambers and arterial trunks. Heart. 2003 Jul;89(7):806-14. PMID: 12807866
  • Bruneau BG. Transcriptional regulation of vertebrate cardiac morphogenesis. Circ Res. 2002 Mar 22;90(5):509-19. Review. PMID: 11909814

UNSW Embryology Links

Development Overview

mouse E9.5 heart (stage 10)

The heart develops from cardiogenic mesoderm that originally lies above the cranial end of the developing neural tube. Enlargement of the cranial neural fold brings this region ventrally to its correct anatomical position. The original paired cardiac tubes fuse, with the "ventricular" primordia initially lying above the "atria". Growth of the cardiac tube flexes it into an "S-shape" tube, rotating the "ventricles" downward and pushing the "atria" upward.

This is then followed by septation, a complex process which converts this simple tube into a four chambered heart and covered in a later lecture and lab. A key part of this process is the separation of cardiac outflow (truncus arteriosus) into a separate pulmonary and aortic arch outflow. During embryonic development there is extensive remodelling of the initially right and left symmetrical cardiovascular system and a contribution from the neural crest to some vessels.



early heart tube
The Human Heart from day 10 to 25 (scanning electron micrograph)



Timecourse

  • forms initially in splanchnic mesoderm of prechordal plate region - cardiogenic region
    • growth and folding of the embryo moves heart ventrallly and downward into anatomical position
  • week 3 begins as paired heart tubes that fuse to form single heart tube
  • begins to beat in Humans- day 22-23
  • heart tube connects to blood vessels forming in splanchnic and extraembryonic mesoderm

Week 2-3 pair of thin -walled tubes

Week 3 tubes fused, truncus arteriosus outflow, heart contracting

Week 4 heart tube continues to elongate, curving to form S shape

Week 5 Septation starts, atrial and ventricular

Septation continues, atrial septa remains open, foramen ovale

Week 37-38 At birth pressure difference closes foramen ovale leaving a fossa ovalis

Angiogenesis

  • blood vessel formation - vasculogenesis
    • also occurs in adult and disease
  • begins week 3 in extraembryonic mesoderm and then embryonic splanchnic mesoderm
  • yolk sac, connecting stalk and chorion
  • growth factors stimulate growth and development - Vascular Endothelial Growth Factor (VEGF)
    • Growing blood vessels follow a gradient generated by target tissues/regions of Vascular Endothelial Growth Factor (VEGF) to establish a vascular bed. Recent findings suggest that Notch signaling acts as an inhibitor for this system, preventing sprouting of blood vessels. Notch is a transmembrane receptor protein involved in regulating cell differentiation in many developing systems.
  • angioblasts form clusters called "blood islands"
  • blood islands extend and fuse together to form a primordial vascular network

Blood Islands

fetal blood
  • 2 populations of cells
    • peripheral- form endothelial cells
    • core- form blood cells (haemocytoblasts)
  • all vessels (arteries and veins) appear initially the same

Blood formation

Mouse hematopoietic stem cell location
  • blood formation from stem cells occurs initially in the extraembryonic mesoderm of the yolk sac
  • then later (week 5) throughout embryonic mesenchyme
  • blood stem cells then migrate into the liver
    • then spleen, bone marrow, lymph nodes

Early Vascular Systems

  • one vascular system with 3 components - vitelline, embryonic (system) and placental
    • each component has own system of artery and vein

Vitelline Blood Vessels

  • cover entire surface of yolk sac, connect to embryo through yolk stalk
  • Arteries - arises from dorsal aorta, contribute to adult GIT arteries
  • Veins - empties into sinus venosus, contribute to the adult portal system

Embryo Blood Vessels

  • (systemic) will form the most of the cardiovascular system
    • some vessels have neural crest contribution
  • Arteries - aortic sac -> aortic arches -> dorsal aorta - umbilical artery
    • dorsal aorta, paired initially and fuses, gives off segmental arteries
  • Veins - 3 pairs of veins empty into the sinus venosus of the heart
    • vitelline, umbilical (only left persists), common cardinal veins
    • cardinal veins - anterior, common, posterior

Placental Blood Vessels

  • form initially in the connecting stalk (then umbilical cord) and anastomose in chorioni
  • extend maternally - toward the chorionic villi
  • extend embryonically - toward the sinus venosus and dorsal aorta
  • Arteries - paired and carry deoxygenated blood (from dorsal aorta) and waste products to the placental villi
  • Veins - paired initially then only left at end of embryonic period and carry oxygenated blood to the embryo (sinus venosus)

Blood flow through the Embryo

Stage13 bloodflow.jpgGray0472.gif

Maternal Blood | -> umbilical vein -> liver -> anastomosis -> sinus venosus -> atria ventricles-> truncus arteriosus -> aortic sac -> aortic arches-> dorsal aorta-> pair of umbilical arteries | Maternal Blood

This is shown on the stage 13/14 pig G6 section. Placenta oxygen exchange levels.jpg

Blood Vessel Remodeling

Cervical intersomitic vessels Gray0473.gif

Heart Development

Early heart cartoon.png
Heart external
Heart internal

MH - Later development of the heart (septation) will be covered in another lecture.

Heart Looping

Heart Looping

Looping.jpg

Transverse section- Heart is 2 tubes that fuse in the midline anterior to pharynx.

The pericardial cavity can be imagined as the top of the "horseshoe" of the intraembryonic coelom. (where the arms become the pleural cavity and the ends fuse anteriorly to form a single peritoneal cavity).

This view shows the initial positioning of the ventricles above the atria. The ventricles are rotated into their correct anatomical position by the growth of the heart tube, bending into an "S" shape.

Initially...

Cardiac inflow- at the bottom (sinus venosus)

Cardiac outflow- at the top (truncus arteriosus)


Heart Neural Crest

  • The mouse model shows that the heart also has contributions from neural crest E8.5 mouse neural crest
    • between the levels of post-otic hindbrain to somite 4, with the most contribution from somite 2 level.
  • 7 somite stage - Migration of cardiac neural crest from the neural tube begins. (level post-otic hindbrain and somite 4)
    • Pathways dorsolateral, medial, and between somites.
    • Then through peri-aortic mesenchyme (lateral to pharynx), through pharyngeal arches (3, 4, 6) into the aortic sac.
  • 32 somite stage: Colonisation of the outflow tract mesenchyme.

Data from: Chan WY, Cheung CS, Yung KM, Copp AJ. Chan WY, Cheung CS, Yung KM, Copp AJ. Cardiac neural crest of the mouse embryo: axial level of origin, migratory pathway and cell autonomy of the splotch (Sp2H) mutant effect. Development. 2004 Jul;131(14):3367-79. PMID: 15226254

Heart Layers

  • pericardium - covers the heart. Formed by 3 layers consisting of a fibrous pericardium and a double layered serous pericardium (parietal layer and visceral epicardium layer).
  • myocardium - muscular wall of the heart. Thickest layer formed by spirally arranged cardiac muscle cells.
  • endocardium - lines the heart. Epithelial tissue lining the inner surface of heart chambers and valves.

Embryonic Heart Rate

Embryonic Heart Rate

  • Ultrasonographic measurement of embryonic heart rate (EHR) shows a steady increase from Stage 9-10 (75 beats/minute) to Stage 18 (130 beats/minute) and on to Stage 20, following which a gradual decrease in EHR occurs
  • Maximal EHR is reached when morphological development of the embryonic heart is completed.

UNSW Embryology Links

Internet Links

Embryo Images Unit: Embryo Images Online Early Cell Populations (cardiogenic section) | Cardiovascular Development | Week 3 Development | Week 4 Development | Heart Chambers and Outflow Tract | Atrioventricular Septation | Outflow Tract Septation | Ventricular Septation | Atrial Septation | Atrial Walls Aortic Arch Vessels | Changes at Birth

References

Textbooks

  • Human Embryology (3rd ed.) Larson Chapter 7 p151-188 Heart, Chapter 8 p189-228 Vasculature
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Chapter 14: p304-349

Other textbooks

  • Before we Are Born (5th ed.) Moore and Persaud Chapter 12; p241-254
  • Essentials of Human Embryology Larson Chapter 7 p97-122 Heart, Chapter 8 p123-146 Vasculature
  • Human Embryology Fitzgerald and Fitzgerald Chapter 13-17: p77-111

Online Textbooks

Reviews

  • Three-dimensional reconstruction of gene expression patterns during cardiac development. Soufan AT, Ruijter JM, van den Hoff MJ, de Boer PA, Hagoort J, Moorman AF. Physiol Genomics. 2003 May 13;13(3):187-95. Review. PMID: 12746463
  • Moorman A, Webb S, Brown NA, Lamers W, Anderson RH. Development of the heart: (1) formation of the cardiac chambers and arterial trunks. Heart. 2003 Jul;89(7):806-14. PMID: 12807866
  • Yutzey KE, Kirby ML. Wherefore heart thou? Embryonic origins of cardiogenic mesoderm. Dev Dyn. 2002 Mar;223(3):307-20. Review. PMID: 11891982
  • Bruneau BG. Transcriptional regulation of vertebrate cardiac morphogenesis. Circ Res. 2002 Mar 22;90(5):509-19. Review. PMID: 11909814

Search

Terms

For more cardiovascular term definitions and links to related topics use the glossary.

angioblast - the stem cells in blood islands generating endothelial cells which will form the walls of both arteries and veins. (More? Blood Vessel)

angiogenesis - the formation of blood vessels also called vasculogenesis in the embryo.

anlage (German, anlage = primordium) structure or cells which will form a future more developed or differentiated adult structure.

blood islands - earliest sites of blood vessel and blood cell formation, seen mainly on yolk sac chorion.

cardinal veins - paired main systemic veins of early embryo, anterior, common, posterior.

cardiogenic region - region above prechordal plate in mesoderm where heart tube initially forms.

ectoderm - the layer (of the 3 germ cell layers) which form the nervous system from the neural tube and neural crest and also generates the epithelia covering the embryo.

endoderm - the layer (of the 3 germ cell layers) which form the epithelial lining of the gastrointestinal tract (GIT) and accessory organs of GIT in the embryo.

endocardium - lines the heart. Epithelial tissue lining the inner surface of heart chambers and valves.

endothelial cells - single layer of cells closest to lumen that line blood vessels.

extraembryonic mesoderm - mesoderm lying outside the trilaminar embryonic disc covering the yolk sac, lining the chorionic sac and forming the connecting stalk. Contributes to placental villi development.

haemocytoblasts - stem cells for embryonic blood cell formation.

anastomose - to connect or join by a connection (anastomosis) between tubular structures.

chorionic villi - the finger-like extensions which are the functional region of the placental barrier and maternal/fetal exchange. Develop from week 2 onward as: primary, secondary, tertiary villi.

estrogens - support the maternal endometrium.

growth factor - usually a protein or peptide that will bind a cell membrane receptor and then activates an intracellular signaling pathway. The function of the pathway will be to alter the cell directly or indirectly by changing gene expression. (eg VEGF, shh)

maternal decidua - region of uterine endometrium where blastocyst implants. undergoes modification following implantation, decidual reaction.

maternal sinusoids - placental spaces around chorionic villi that are filled with maternal blood. Closest maternal/fetal exchange site.

mesoderm - the middle layer of the 3 germ cell layers of the embryo. Mesoderm outside the embryo and covering the amnion, yolk and chorion sacs is extraembryonic mesoderm.

myocardium - muscular wall of the heart. Thickest layer formed by spirally arranged cardiac muscle cells.

pericardium - covers the heart. Formed by 3 layers consisting of a fibrous pericardium and a double layered serous pericardium (parietal layer and visceral epicardium layer).

pharyngeal arches (=branchial arches, Gk. gill) series of cranial folds that form most structures of the head and neck. Six arches form but only 4 form any structures. Each arch has a pouch, membrane and groove.

placenta - (Greek, plakuos = flat cake) refers to the discoid shape of the placenta, embryonic (villous chorion)/maternal organ (decidua basalis)

placental veins - paired initially then only left at end of embryonic period, carry oxygenated blood to the embryo (sinus venosus).

protein hormone - usually a protein distributed in the blood that binds to membrane receptors on target cells in different tissues. Do not easliy cross placental barrier.

sinus venosus - cavity into which all major embryonic paired veins supply (vitelline, placental, cardinal).

splanchnic mesoderm - portion of lateral plate mesoderm closest to the endoderm when coelom forms.

steroid hormone - lipid soluble hormone that easily crosses membranes to bind receptors in cytoplasm or nucleus of target cells. Hormone+Receptor then binds DNA activating or suppressing gene transcription. Easliy cross placental barrier.

syncitiotrophoblast extraembryonic cells of trophoblastic shell surrounding embryo, outside the cytotrophoblast layer, involved with implantation of the blastocyst by eroding extracellular matrix surrounding maternal endometrial cells at site of implantation, also contribute to villi. (dark staining, multinucleated).

vascular endothelial growth factor - (VEGF) protein growth factor family that stimulates blood vessel growth, a similar factor can be found in the placenta (PIGF).

vitelline blood vessels - blood vessels associated with the yolk sac.

waste products - products of cellular metabolism and cellular debris, e.g.- urea, uric acid, bilirubin.

Glossary Links

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Cite this page: Hill, M.A. (2024, March 28) Embryology 2009 Lecture 7. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/2009_Lecture_7

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