Cardiovascular System Development
Embryology - 1 Dec 2023 ![]() ![]() ![]() |
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Introduction
Development of the heart and vascular system is often described together as the cardiovascular system, with the heart being the first functional organ that forms in the embryo. Development begins very early in mesoderm both within (embryonic) and outside (extra embryonic, yolk sac and placental) the embryo. Vascular development therefore occurs in many places, the most obvious though is the early forming heart, which grows rapidly creating an externally obvious cardiac "bulge" on the early embryo. The cardiovascular system is extensively remodelled throughout development, this current page only introduces topic.
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.
Throughout the mesoderm, small regions differentiate into "blood islands" which contribute both blood vessels (walls) and fetal red blood cells.
These "islands" connect together to form the first vessels which connect with the heart tube.
A detailed description of heart development is covered in the Online Heart Tutorial.
Some Recent Findings
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More recent papers |
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This table allows an automated computer search of the external PubMed database using the listed "Search term" text link.
More? References | Discussion Page | Journal Searches | 2019 References | 2020 References Search term: Cardiovascular Embryology | Cardiovascular Development |
Older papers |
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These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.
See also the Discussion Page for other references listed by year and References on this current page.
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Textbooks
- 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
Heart Tutorial
Begin Basic | Primitive Heart Tube | Embryonic Heart Divisions | Vascular Heart Connections |
Begin Intermediate: | Primordial Heart Tube | Heart Tube Looping | Atrial Ventricular Septation | Outflow Tract | Heart Valves | Cardiac Abnormalities | Vascular Overview |
Begin Advanced | Heart Fields | Heart Tubes | Cardiac Looping | Cardiac Septation | Outflow Tract | Valve Development | Cardiac Conduction | Cardiac Abnormalities | Molecular Development |
Timecourse
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The Human Heart from day 10 to 25 (scanning electron micrograph) |
- Forms initially in splanchnic mesoderm of prechordal plate region - cardiogenic region
- growth and folding of the embryo moves heart ventrally and downward into anatomical position
- Day 22 - 23, begins to beat in humans
- heart tube connects to blood vessels forming in splanchnic and extraembryonic mesoderm
- Week 2 - 3 pair of thin-walled tubes
- Week 3 paired heart tubes fuse, 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
Characteristic | Carnegie stage: | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 |
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Septum primum | ||||||||||||
Foramen primum | ||||||||||||
Atrioventricular bundle | ||||||||||||
Atrioventricular cushions | ||||||||||||
Conotruncal ridges | ||||||||||||
Foramen secundum | ||||||||||||
Semilunar cusps | ||||||||||||
Conotruncal septum; atria | ||||||||||||
Closure primum foramen | ||||||||||||
Fusion atrioventricular cushions | ||||||||||||
Septum secundum and foramen ovale | ||||||||||||
Closure secondary interventricular foramen | ||||||||||||
Chordae tendineae | ||||||||||||
Colour Coding: | beginning to appear | present | Table data[5] Links: heart | Madrid Collection |
Heart Development Movies
Animations
Animations showing aspects of heart development.
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Tutorials
Pages within the online Cardiac tutorial.
Heart Cartoons | |||||||||||||||||||||||||||
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Historic
Historic animations including audio descriptions. Some of these descriptions may be currently inaccurate, the transfer is from an old class film and the audio track is of very poor quality.
Historic Animations | |||||||||||||||
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About Historic Animations | ||||
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Animations are modified and converted from a historic film (circa 1960's, copyright unknown) demonstrating aspects of human heart development.
The sound quality is quite poor and some of the information is now out of date, most general concepts are still correct. Please note the relatively large size (Mb) of each excerpt will effect download and viewing. March 2013
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Septation Models
Ventricular septation rotation models.
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Animal Models
Amphibians and reptiles have a three-chambered heart with a single ventricle. Blood leaves the heart ventricle through either the pulmonary artery to the lungs or the aorta to supply the body. The pulmonary artery in amphibians also supplies the skin.
Mammals and birds have a four-chambered heart with a two ventricles. The right ventricle supplies the pulmonary artery to the lungs, the left ventricle supplies the aorta to the body.
Chicken Heart Development
Note the images of chicken heart development[6] shown below are Hamburger Hamilton Stages of chicken development, not Carnegie stages. See also Heart 3D reconstruction.
Pharyngeal Arch Arteries
In the head region of the embryo, each pharyngeal arch initially has paired arch arteries. These are extensively remodelled through development and give rise to a range of different arterial structures, as shown in the list below.
- Arch 1 - mainly lost, form part of maxillary artery.
- Arch 2 - stapedial arteries.
- Arch 3 - common carotid arteries, internal carotid arteries.
- Arch 4 - left forms part of aortic arch, right forms part right subclavian artery.
- Arch 6 - left forms part of left pulmonary artery , right forms part of right pulmonary artery.
- Links: Head Development
Renal Venous Development
The renal arterial and venous systems are also reorganised extensively throughout development with changing kidney position.
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Embryo renal venous | Adult renal venous |
- Links: Renal Development
Fetal Blood Flow
Mean Late Fetal Blood Flows[7]
(8 subjects) in the major vessels of the human fetal circulation by phase contrast MRI. (median gestational age 37 weeks, age range of 30–39 weeks)
(left) Mean flows in ml/kg/min | (right) Proportions of the combined ventricular output in the major vessels of the human fetal circulation by phase contrast MRI. |
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- Cardiovascular Links: Fetal Blood Flow values | Mean Fetal Blood Flow | Proportions Ventricular Output | Ventricular Output (colour) | heart | blood | cardiovascular
References
- ↑ Anderson RH, Mori S, Spicer DE, Brown NA & Mohun TJ. (2016). Development and Morphology of the Ventricular Outflow Tracts. World J Pediatr Congenit Heart Surg , 7, 561-77. PMID: 27587491 DOI.
- ↑ Krishnan A, Samtani R, Dhanantwari P, Lee E, Yamada S, Shiota K, Donofrio MT, Leatherbury L & Lo CW. (2014). A detailed comparison of mouse and human cardiac development. Pediatr. Res. , 76, 500-7. PMID: 25167202 DOI.
- ↑ Vreeker A, van Stuijvenberg L, Hund TJ, Mohler PJ, Nikkels PG & van Veen TA. (2014). Assembly of the cardiac intercalated disk during pre- and postnatal development of the human heart. PLoS ONE , 9, e94722. PMID: 24733085 DOI.
- ↑ Ishii Y, Langberg J, Rosborough K & Mikawa T. (2009). Endothelial cell lineages of the heart. Cell Tissue Res. , 335, 67-73. PMID: 18682987 DOI.
- ↑ Arráez-Aybar LA, Turrero-Nogués A & Marantos-Gamarra DG. (2008). Embryonic cardiac morphometry in Carnegie stages 15-23, from the Complutense University of Madrid Institute of Embryology Human Embryo Collection. Cells Tissues Organs (Print) , 187, 211-20. PMID: 18057862 DOI.
- ↑ van den Berg G & Moorman AF. (2011). Development of the pulmonary vein and the systemic venous sinus: an interactive 3D overview. PLoS ONE , 6, e22055. PMID: 21779373 DOI.
- ↑ Seed M, van Amerom JF, Yoo SJ, Al Nafisi B, Grosse-Wortmann L, Jaeggi E, Jansz MS & Macgowan CK. (2012). Feasibility of quantification of the distribution of blood flow in the normal human fetal circulation using CMR: a cross-sectional study. J Cardiovasc Magn Reson , 14, 79. PMID: 23181717 DOI.
Reviews
Jensen B, Spicer DE, Sheppard MN & Anderson RH. (2017). Development of the atrial septum in relation to postnatal anatomy and interatrial communications. Heart , 103, 456-462. PMID: 28003417 DOI.
Kelly RG. (2012). The second heart field. Curr. Top. Dev. Biol. , 100, 33-65. PMID: 22449840 DOI.
Carmeliet P & Jain RK. (2011). Molecular mechanisms and clinical applications of angiogenesis. Nature , 473, 298-307. PMID: 21593862 DOI.
Degani S. (2008). Fetal cerebrovascular circulation: a review of prenatal ultrasound assessment. Gynecol. Obstet. Invest. , 66, 184-96. PMID: 18607112 DOI.
Tchirikov M, Schröder HJ & Hecher K. (2006). Ductus venosus shunting in the fetal venous circulation: regulatory mechanisms, diagnostic methods and medical importance. Ultrasound Obstet Gynecol , 27, 452-61. PMID: 16565980 DOI.
Kiserud T. (2005). Physiology of the fetal circulation. Semin Fetal Neonatal Med , 10, 493-503. PMID: 16236564 DOI.
Kiserud T & Acharya G. (2004). The fetal circulation. Prenat. Diagn. , 24, 1049-59. PMID: 15614842 DOI.
Articles
Jiji RS & Kramer CM. (2011). Cardiovascular magnetic resonance: applications in daily practice. Cardiol Rev , 19, 246-54. PMID: 21808168 DOI.
Ribatti D & Djonov V. (2011). Angiogenesis in development and cancer today. Int. J. Dev. Biol. , 55, 343-4. PMID: 21732277 DOI.
Cammarato A, Ahrens CH, Alayari NN, Qeli E, Rucker J, Reedy MC, Zmasek CM, Gucek M, Cole RN, Van Eyk JE, Bodmer R, O'Rourke B, Bernstein SI & Foster DB. (2011). A mighty small heart: the cardiac proteome of adult Drosophila melanogaster. PLoS ONE , 6, e18497. PMID: 21541028 DOI.
Min JK, Park H, Choi HJ, Kim Y, Pyun BJ, Agrawal V, Song BW, Jeon J, Maeng YS, Rho SS, Shim S, Chai JH, Koo BK, Hong HJ, Yun CO, Choi C, Kim YM, Hwang KC & Kwon YG. (2011). The WNT antagonist Dickkopf2 promotes angiogenesis in rodent and human endothelial cells. J. Clin. Invest. , 121, 1882-93. PMID: 21540552 DOI.
Guo C, Sun Y, Zhou B, Adam RM, Li X, Pu WT, Morrow BE, Moon A & Li X. (2011). A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis. J. Clin. Invest. , 121, 1585-95. PMID: 21364285 DOI.
Arráez-Aybar LA, Turrero-Nogués A & Marantos-Gamarra DG. (2008). Embryonic cardiac morphometry in Carnegie stages 15-23, from the Complutense University of Madrid Institute of Embryology Human Embryo Collection. Cells Tissues Organs (Print) , 187, 211-20. PMID: 18057862 DOI.
Search Pubmed
Search Pubmed: Cardiovascular System Development
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Additional Images
See also Category:Heart ILP and Category:Heart
External Links
External Links Notice - The dynamic nature of the internet may mean that some of these listed links may no longer function. If the link no longer works search the web with the link text or name. Links to any external commercial sites are provided for information purposes only and should never be considered an endorsement. UNSW Embryology is provided as an educational resource with no clinical information or commercial affiliation.
- Australia Heart Foundation
- USA National Heart, Lung, and Blood Institute - Congenital Heart Defects | Heart and Vascular Information
System Links: Introduction | Cardiovascular | Coelomic Cavity | Endocrine | Gastrointestinal Tract | Genital | Head | Immune | Integumentary | Musculoskeletal | Neural | Neural Crest | Placenta | Renal | Respiratory | Sensory | Birth |
Terms
- angioblastic cords - Groups or ‘columns’ of embryonic precursor cells which will form the walls of both arteries and veins.
- apex - Anatomical term referring to the most inferior, left, downwards pointing part of the heart.
- aorta - The largest artery in the human body originating in the left ventricle. The aorta ascends, arches over the heart and then descends through the abdomen.
- aortic arch arteries - (pharyngeal arch arteries) Each early developing pharyngeal arch contains a lateral pair of arteries arising from the aortic sac, above the heart, and running into the dorsal aorta. Later in development these arch arteries are extensively remodelled to form specific components of the vascular system.
- aortic valve - Three-leaflet valve located at the junction between the left ventricle and aortic entrance.
- aortic vestibule - Smooth-walled portion of the left ventricle directly below the aortic valve.
- aorticopulmonary septum - Division between the aorta and the pulmonary trunk formed from the bulbar ridges.
- atresia - Abnormal closure or absence of a body vessel or orifice.
- atrioventricular canal - Junction between the primitive atrium and primitive ventricle in the embryo. This canal splits to later form two atrioventricular canals which consequently form the valves of the adult heart.
- bulbar ridges - Endocardial cushion tissue located in the bulbus cordis extending into the truncus arteriosus thus forming ridges. These fuse together to form the aorticopulmonary septum.
- bulbus cordis - A region of the early developing heart tube forming the common outflow tract, will differentiate to form three regions of the heart.
- cardiac jelly - Term used in early heart development to describe the initial gelatinous or sponge-like connective tissue separating the myocardium and heart tube endothelium.
- cardiogenic region - The area in the embryo where the precursor cells for heart development lie.
- chordae tendineae - Cord-like tendons connecting the papillary muscles to the leaflets of the mitral and tricuspid valves.
- congenital heart disease - Abnormal structure or function of the heart due to a developmental defect arising prior to birth.
- connective tissue - Fibrous tissue that acts to support body structures or bind other forms of tissue.
- conus arteriosus - An embryological heart outflow structure, that forms in early cardiac development and will later divides into the pulmonary artery and aorta. Term is also used clinically to describe the malformation of the cardiac outflow pattern, where only one artery arises from the heart and forms the aorta and pulmonary artery.
- coronary sinus - a venous sinus emptying into the right atrium that collects blood from the myocardium of the heart. The coronary sinus is the largest cardiac vein.
- cyanosis - Blue colouration of the skin and mucous membrane due to poor oxygenation of the blood.
- dorsal aortae - Two largest arteries either side of the midline which later fuse to form the descending portion of the aorta.
- dorsal mesocardium - The mesentery attaching the heart to the dorsal wall of the pericardial coelom. This breaks down to form a space known as the transverse pericardial sinus.
- dyspnoea - Shortness of breath.
- endocardial cushions - Swellings of migrated cells on the inner lining of the heart located in the atrioventricular canal.
- endocardial heart tubes - Two tubes formed from the cardiogenic plate in the developing embryo. These form the primordium of the truncus arteriosus, the atrium and the ventricles; later invested with myocardium.
- endocardium - The epithelial membrane lining the inside surface of heart, which along with the endothelial layer forms a continuous lining of the entire cardiovascular system. The endocardium, like the majority of the heart is mesoderm in origin.
- endothelium - A simple squamous epithelium lining blood vessels.
- epicardium - The outer layer of heart tissue.
- fibrous trigone - (trigonum fibrosum) term describing the dense connective tissue between the aortic ring and the atrioventricular ring and has a left and right component. The right fibrous trigone (trigonum fibrosum dextrum) lies between the aortic ring and the right atrioventricular ring. The left fibrous trigone (trigonum fibrosum sinistrum) lies between the aortic ring and the left atrioventricular ring.
- foramen ovale - Shunt allowing blood to enter the left atrium from the right atrium. It is located in the septum secundum.
- foramen primum - Original space between the septum primum and the fused endocardial cushions as the septum primum grows towards the cushions.
- foramen secundum - Refers to the coalesced perforations in the septum primum after it has fused with the endocardial cushions.
- fossa ovalis - (oval fossa, annulus ovalis) Region in the postnatal atrial septum where the foramen ovale was located during embryonic development. Appears as an indentation in the right atrium septum.
- heart murmur - Extra heart sounds appearing upon auscultation due to turbulent blood flow.
- hypertrophy - Increase in size of an organ or tissue due to enlargement of component cells.
- inferior vena cava - (IVC) Large vein which carries deoxygenated blood from the lower half of the body to the right atrium.
- inflow tract - Entrance of blood into the heart tube; the sinus venosus portion of the tube.
- infundibulum - Smooth-walled portion of the right ventricle directly below the pulmonary valve.
- interventricular septum - Wall of muscular tissue growing from the base of the heart dividing the primitive ventricle into the left and right ventricles.
- interventricular foramen - Space between the interventricular septum and the fused endocardial cushions. The foramen closes when the septum fuses with the endocardial cushions and bulbar ridges.
- intraembryonic coelom - Initial embryonic space in lateral plate mesoderm that will be separated to form the three major body cavities: pericardial, pleural and peritoneal cavity. The lateral plate mesoderm is divided by this space into splanchnic and somatic mesoderm.
- left horn of sinus venosus - The left side of the sinus venosus (initially symmetrical with the right) collecting blood from half of the paired veins: common cardinal veins, umbilical veins and vitelline veins. Later the left horn diminishes and becomes the small coronary sinus.
- mitral valve - (Bicuspid valve) two leaflet valve located on the left side of the heart, that is between the left atrium and ventricle.
- myocardium - The middle layer of the heart wall composed of cardiac muscle.
- neural crest mesenchyme - Connective tissue arising from critical cells in the cranial region of the embryo. These paired dorsal lateral streaks of cells migrate throughout the embryo and can differentiate into many different cell types (= pluripotential). Those that remain on the dorsal neural tube form the sensory spinal ganglia (DRG), those that migrate ventrally form the sympatheitic ganglia. Neural crest cells also migrate into the somites and regions through the entire embryo.
- outflow tract - Exit of blood from the heart tube formed by the truncus arterioles.
- oval fossa - (fossa ovalis, annulus ovalis) Region in the postnatal atrial septum where the foramen ovale was located during development. Appears as an indentation in the right atrium septum.
- papillary muscles - Small muscles found on the inner myocardium of the left and right ventricles. They are attached to the mitral and tricuspid valves via the chordae tendineae and serve to limit the movements of the valves.
- patent foramen ovale - Abnormality in atrial septum due to failure of the atrial septum to close at the foramen ovale. (More? Atrial Septal Defects)
- pericardial coelom - (pericardial cavity) The anatomical body cavity in which the heart lies. The pericardial cavity forms in the lateral plate mesoderm above the buccopharyngeal membrane, as part of the early intraembryonic coelom. This cavity is initially continuous with the two early pleural cavities. Note the single intraembryonic coelom forms all three major body cavities: pericardial cavity, pleural cavity, peritoneal cavity.
- primordial atrium - Common cavity in the upper portion of the developing heart. Later divides to form the left and right atria.
- primordial ventricle - Common cavity in the lower portion of the developing heart. Later divides to form the left and right ventricles.
- pulmonary circulation - Carries blood between the heart and lungs.
- pulmonary trunk - A vessel that arises from the right ventricle of the heart, extends upward, and divides into the right and left pulmonary arteries that transport deoxygenated blood to the lungs.
- pulmonary valve - Three-leaflet valve located at the junction between the right ventricle and the pulmonary trunk.
- pulmonary veins - Four veins that allow oxygenated blood from the lungs to empty into the left atrium.
- right horn of sinus venosus - The right side of the sinus venosus (initially symmetrical with the left) collecting blood from half of the paired veins: common cardinal veins, umbilical veins and vitelline veins. Later the right horn dilates, receiving all the veins, and becomes the sinus venarum of the right atrium.
- second heart field - (SHF) splanchnic mesoderm that forms progenitors important for heart formation.
- semilunar valves - Flaps of endocardium and connective tissue reinforced by fibres which prevent the valves from turning inside out. They are shaped like a half moon, hence the name semilunar. The semilunar valves are located between the aorta and the left ventricle and between the pulmonary artery and the right ventricle.
- septum primum - Original structure growing from the roof of the heart towards the endocardial cushions dividing the primitive atrium.
- septum secundum - Second structure growing to the right of the septum primum dividing the primitive atrium.
- sinoatrial node - Specialised cardiomyocyte pacemaking region of the heart located at the entry of the right superior caval vein (SVC) into the right atrium. (More? Detailed Cardiac - Sinus Node)
- sinus venosus - (systemic venous sinus) An early developmental cardiovascular structure, thin walled cavity, forming the input to developing heart which has 3 venous inputs (vitelline vein, umbilical vein, common cardinal vein). Later in heart development this structure gets incorporated into the wall of the future right atrium. (More? Systemic Venous Sinus)
- sinuatrial orifice - The opening between the sinus venosus and right atrium which has two valve leaflets to prevent backflow of blood.
- sinus venarum - Smooth-walled portion of the adult right atrium; originally the left horn of the sinus venous.
- splanchnic mesoderm - Gastrointestinal tract (endoderm) associated mesoderm formed by the separation of the lateral plate mesoderm into two separate components by a cavity, the intraembryonic coelom. Splanchnic mesoderm is the embryonic origin of the second heart field, gastrointestinal tract connective tissue, smooth muscle, blood vessels and contribute to organ development (heart, pancreas, spleen, liver).
- stenosis - Abnormal narrowing of a blood vessel or orifice.
- superior vena cava - (SVC) Short vein which carries deoxygenated blood from the upper half of the body to the right atrium.
- systemic circulation - Carries oxygenated blood away from the heart to the other body organs and returns to the heart deoxygenated.
- tachypnoea - Abnormally rapid breathing rate.
- trabeculae - (trabeculations)Muscular beams located within the ventricles and parts of the atria of the heart.
- transverse pericardial sinus - Dorsal area within the pericardial coelom, initially occupied by the dorsal mesocardium.
- tricuspid valve - Three leaflet valve located in the right atrioventricular canal i.e. between the right atrium and ventricle.
- tricuspid atresia - Abnormality of the tricuspid valve between the right atrium and right ventricle.
- truncus arteriosus - An embryological heart outflow structure, that forms in early cardiac development and will later divides into the pulmonary artery and aorta. Term is also used clinically to describe the malformation of the cardiac outflow pattern, where only one artery arises from the heart and forms the aorta and pulmonary artery.
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Cite this page: Hill, M.A. (2023, December 1) Embryology Cardiovascular System Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Cardiovascular_System_Development
- © Dr Mark Hill 2023, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G