UNSW Embryology

Cardiovascular System Development

© Dr Mark Hill (2011)

Acknowledgements

Introduction

These notes introduce the development of the heart which begins very early in mesoderm within the trilaminar embryonic disc. The heart forms initially in the embryonic disc as a simple paired tube inside the forming pericardial cavity, which when the disc folds, gets carried into the correct anatomical position in the chest cavity.	Stage 11 embryo heart bulge
A key aspect of heart development is the septation of the heart into separate chambers. As the embryonic/fetal circulation is different to the neonatal circulation (lung/pulmonary activation), several defects of heart septation may only become apparent on this transition. One septal "defect" occurs in us all, the foramen ovale (between the 2 atria) which in general closes in the neonate over time.	Stage 13 heart cross-section

Embryonic Heart Rate (EHR), early in development the heart starts to spontaneously beat and a recent study by Wisser and Dirschedl in dated human embryos showed an increase up to 63 postmenstrual days or 22 mm greatest length. Thereafter a steady decrease of EHR was noted. Maximal EHR is reached when morphological development of the embryonic heart is completed. (see EHR Page).

Page Links: Introduction | Reading | Computer Activities | Objectives | Learning activities | Development Overview | Early Heart Development | Heart Layers | Heart Volume | References | Glossary | Terms |

Related Pages: Abnormalities | Stage 13/14 | Stage 22 | Stage 22 Selected Highpower | Heart Rate | Blood | Blood Vessels | Molecular | Lymphatic | Placenta

Some Recent Findings

Molina FS, Faro C, Sotiriadis A, Dagklis T, Nicolaides KH. Heart stroke volume and cardiac output by four-dimensional ultrasound in normal fetuses. Ultrasound Obstet Gynecol. 2008 Aug;32(2):181-7.

"In normal fetuses the stroke volume and cardiac output increase between 12 and 34 weeks' gestation. The extent to which, in pathological pregnancies, possible deviations in these measurements from normal prove to be useful in the prediction of outcome remains to be determined."

Watanabe Y, Kokubo H, Miyagawa-Tomita S, Endo M, Igarashi K, Aisaki KI, Kanno J, Saga Y. Activation of Notch1 signaling in cardiogenic mesoderm induces abnormal heart morphogenesis in mouse. Development. 2006 May;133(9):1625-34.

"...Our present study thus indicates that the Notch1 signaling pathway plays a suppressive role both in AV myocardial differentiation and the maturation of the ventricular myocardium." (More? Notch Notes)

Development Timecourse

• Cardiogenic region - in splanchnic mesenchyme of prechordal plate region
• Week 2 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 40 At birth pressure difference closes foramen ovale leaving a fossa ovalis

Early Heart Development

	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 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.

Heart Volume

*Table data is "embryonic age" while original reference used "gestational age" (from LMP)
(Data: Peralta CF, Cavoretto P, Csapo B, Falcon O, Nicolaides KH. Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12-32 weeks' gestation. Ultrasound Obstet Gynecol. 2006 Feb;27(2):128-33.)

Stroke Volume

*Table data is "embryonic age" while original reference used "gestational age" (from LMP). The stroke volume (SV) can be calculated from ultrasound measurement of end diastole volume (EDV) minus end systole volume (ESV); (SV = EDV - ESV).
(Data: Molina FS, Faro C, Sotiriadis A, Dagklis T, Nicolaides KH. Heart stroke volume and cardiac output by four-dimensional ultrasound in normal fetuses. Ultrasound Obstet Gynecol. 2008 Aug;32(2):181-7.

Reading

Textbook

• Human Embryology (2nd ed.) Larson Ch7 p151-188 Heart, Ch8 p189-228 Vasculature
• The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Ch14: p304-349
• Before we Are Born (5th ed.) Moore and Persaud Ch12; p241-254
• Essentials of Human Embryology Larson Ch7 p97-122 Heart, Ch8 p123-146 Vasculature
• Human Embryology Fitzgerald and Fitzgerald Ch13-17: p77-111

Medline

• Wherefore heart thou? Embryonic origins of cardiogenic mesoderm
• The anterior heart-forming field: voyage to the arterial pole of the heart
• Development of the heart: (1) formation of the cardiac chambers and arterial trunks (2003)
• Development of the heart: (2) Septation of the atriums and ventricles (2003)

Search PubMed- Medline

(More? Additional References)

Computer Activities

UNSW Embryology: Stage 13/14 Embryo | venous inflow to the heart | ventricles into the aortic system | caudal path of the arterial blood | embryo's venous blood | Stage 22 Embryo | Stage 22 Selected High power | Pig Systems | Human Systems (Human Cardiac) | Cardiovascular Abnormalities | Stage 16 (E12.5 Mouse vascular) | Molecular Development | Blood Development | Postnatal Heart Development | ILP Heart Tutorial

Heart Movies: Heart Development Movie Page | Heart Septation | Historic Heart Movie

Heart Looping (451Kb)	Atrial Septation (995Kb)	Realignment (306Kb)	Ventricular Septation (646Kb)

Fetal Circulation (Before Birth) (1Mb)	Circulation (After Birth) (561Kb)

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

• Person AD, Klewer SE, Runyan RB. Cell biology of cardiac cushion development. Int Rev Cytol. 2005;243:287-335. Review.

• Matsui H, Ikeda K, Nakatani K, Sakabe M, Yamagishi T, Nakanishi T, Nakajima Y. Induction of initial cardiomyocyte alpha-actin--smooth muscle alpha-actin--in cultured avian pregastrula epiblast: a role for nodal and BMP antagonist. Dev Dyn. 2005 Aug;233(4):1419-29.
• 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.
• Anderson RH, Webb S, Brown NA, Lamers W, Moorman A. Development of the heart: (2) Septation of the atriums and ventricles. Heart. 2003 Aug;89(8):949-58.
• Brand T. Heart development: molecular insights into cardiac specification and early morphogenesis. Dev Biol. 2003 Jun 1;258(1):1-19.
• Yutzey KE, Kirby ML. Wherefore heart thou? Embryonic origins of cardiogenic mesoderm. Dev Dyn. 2002 Mar;223(3):307-20.
• Eisenberg LM. Belief vs. scientific observation: the curious story of the precardiac mesoderm. Anat Rec. 2002 Apr 1;266(4):194-7.
• Davidson AJ, Zon LI. Turning mesoderm into blood: the formation of hematopoietic stem cells during embryogenesis. Curr Top Dev Biol. 2000;50:45-60.

Selected Lists of References from PubMed March 1999 search results are available for School of Anatomy computers without internet access. Computers with internet access can search from either Page 2 or PubMed Internet Access

• Selected Research Articles and Reviews
• "Heart/review/5year limit"
• "Cardiovascular/Development/2year limit"

Search Pubmed Now

Click on the listed keywords below (used to search the external database) the most current references on Medline will be displayed.

• heart[TITL]+development[WORD]+review[WORD]

Glossary of Terms

A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z | Numbers | Old Glossary

Cardiovascular Development Terms

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

• anlage (Ger. ) primordium, structure or cells which will form a future structure.
• atrial septal defects (A.S.D.)
• cardinal veins paired main systemic veins of early embryo, anterior, common, posterior.
• cardiogenic region region above precordal plate in mesoderm where ceart tube initially forms.
• 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
• anastomose-
• 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)
• 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.
• neural crest cell region at edge of neural plate, then atop the neural folds, that remains outside and initially dorsal to the neural tube when it forms. These paired dorsal lateral streaks of cells migrate throughout the embryo and can differentiate into many different cell types(=pluripotential). Neural crest cells also contribute to major cardiac outflow vessels.
• patent ductus arteriosus (P.D.A.)
• 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) form structures of the head. Six arches form but only 4 form any structures. Each arch has a pouch, membrane and groove.
• 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.
• tetralogy of Fallot- Named after Etienne-Louis Arthur Fallot (1888) who described it as "la maladie blue". The syndrome consists of a number of a number of cardiac defects possibly stemming from abnormal neural crest migration.
• vascular endothelial growth factor (VEGF) protein growth factor family that stimulates blood vessel growth, a similar factor can be found in the placenta (PIGF).
• ventricular septal defects (V.S.D.)
• virus small infectious agent able to cross placental barrier. Can infect embryo and cause developmental abnormalities. (e.g. cytomegalovirus, rubella, measles)

Quick Links

Page 2 | Abnormalities | OMIM | Questions | Medline
Page 3 | Pig Stage 13/14
Page 4 | Human (Stage22) | Selected Human highpower
Molecular | Lymphatic | Blood | Text only page | WWW Links | Heart Movies | Postnatal Heart Development

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