Cardiovascular System Development

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Heart Tube Fusion.jpg


The embryo stage 10 heart tube

Development of the heart and vascular system 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.

Cardiovascular Links: Introduction | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | Heart | Coronary Circulation | Heart Valve | Heart Rate | Circulation | Blood | Blood Vessel | Blood Vessel Histology | Cardiac Muscle Histology | Lymphatic | Ductus Venosus | Spleen | Stage 22 | Abnormalities | OMIM | ECHO Meeting | Category:Cardiovascular
Historic Embryology
1912 Heart | 1912 Human Heart | 1915 Congenital Cardiac Disease | 1916 Pars Membranacea Septi | 1921 Human Brain Vascular | 1923 Head Subcutaneous Plexus | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1938 Pars Membranacea Septi | Ziegler Heart Models | Historic Disclaimer

Some Recent Findings

  • A detailed comparison of mouse and human cardiac development[1] "Episcopic fluorescence image capture (EFIC) was performed on 66 wild-type mouse embryos from embryonic day (E) 9.5 to birth; 2-dimensional and 3-dimensional datasets were compared with EFIC and magnetic resonance images from a study of 52 human fetuses (Carnegie stage 13-23). Time course of atrial, ventricular, and outflow septation were outlined and followed a similar sequence in both species. Bilateral venae cavae and prominent atrial appendages were seen in the mouse fetus; in human fetuses, atrial appendages were small, and a single right superior vena cava was present. In contrast to humans with separate pulmonary vein orifices, a pulmonary venous confluence with one orifice enters the left atrium in mice. The cardiac developmental sequences observed in mouse and human fetuses are comparable, with minor differences in atrial and venous morphology. These comparisons of mouse and human cardiac development strongly support that mouse morphogenesis is a good model for human development." Mouse Development | Kyoto Collection
  • Assembly of the Cardiac Intercalated Disk during Pre- and Postnatal Development of the Human Heart[2] "In cardiac muscle, the intercalated disk (ID) at the longitudinal cell-edges of cardiomyocytes provides as a macromolecular infrastructure that integrates mechanical and electrical coupling within the heart. ...Our data on developmental maturation of the ID in human heart indicate that generation of the mechanical junctions at the ID precedes that of the electrical junctions with a significant difference in time. In addition arrival of the electrical junctions (Nav1.5 and Cx43) is not uniform since sodium channels localize much earlier than gap junction channels."
  • Endothelial cell lineages of the heart. [3] "During early gastrulation, vertebrate embryos begin to produce endothelial cells (ECs) from the mesoderm. ECs first form primitive vascular plexus de novo and later differentiate into arterial, venous, capillary, and lymphatic ECs. In the heart, the five distinct EC types (endocardial, coronary arterial, venous, capillary, and lymphatic) have distinct phenotypes. For example, coronary ECs establish a typical vessel network throughout the myocardium, whereas endocardial ECs form a large epithelial sheet with no angiogenic sprouting into the myocardium. Neither coronary arteries, veins, and capillaries, nor lymphatic vessels fuse with the endocardium or open to the heart chamber. The developmental stage during which the specific phenotype of each cardiac EC type is determined remains unclear. The mechanisms involved in EC commitment and diversity can however be more precisely defined by tracking the migratory patterns and lineage decisions of the precursors of cardiac ECs."
More recent papers
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches

Search term: Cardiovascular Embryology

Mateusz Olbromski, Jedrzej Grzegrzolka, Alina Jankowska-Konsur, Wojciech Witkiewicz, Marzena Podhorska-Okolow, Piotr Dziegiel MicroRNAs modulate the expression of the SOX18 transcript in lung squamous cell carcinoma. Oncol. Rep.: 2016; PubMed 27666488

Pim van der Harst, Jessica van Setten, Niek Verweij, Georg Vogler, Lude Franke, Matthew T Maurano, Xinchen Wang, Irene Mateo Leach, Mark Eijgelsheim, Nona Sotoodehnia, Caroline Hayward, Rossella Sorice, Osorio Meirelles, Leo-Pekka Lyytikäinen, Ozren Polašek, Toshiko Tanaka, Dan E Arking, Sheila Ulivi, Stella Trompet, Martina Müller-Nurasyid, Albert V Smith, Marcus Dörr, Kathleen F Kerr, Jared W Magnani, Fabiola Del Greco M, Weihua Zhang, Ilja M Nolte, Claudia T Silva, Sandosh Padmanabhan, Vinicius Tragante, Tõnu Esko, Gonçalo R Abecasis, Michiel E Adriaens, Karl Andersen, Phil Barnett, Joshua C Bis, Rolf Bodmer, Brendan M Buckley, Harry Campbell, Megan V Cannon, Aravinda Chakravarti, Lin Y Chen, Alessandro Delitala, Richard B Devereux, Pieter A Doevendans, Anna F Dominiczak, Luigi Ferrucci, Ian Ford, Christian Gieger, Tamara B Harris, Eric Haugen, Matthias Heinig, Dena G Hernandez, Hans L Hillege, Joel N Hirschhorn, Albert Hofman, Norbert Hubner, Shih-Jen Hwang, Annamaria Iorio, Mika Kähönen, Manolis Kellis, Ivana Kolcic, Ishminder K Kooner, Jaspal S Kooner, Jan A Kors, Edward G Lakatta, Kasper Lage, Lenore J Launer, Daniel Levy, Alicia Lundby, Peter W Macfarlane, Dalit May, Thomas Meitinger, Andres Metspalu, Stefania Nappo, Silvia Naitza, Shane Neph, Alex S Nord, Teresa Nutile, Peter M Okin, Jesper V Olsen, Ben A Oostra, Josef M Penninger, Len A Pennacchio, Tune H Pers, Siegfried Perz, Annette Peters, Yigal M Pinto, Arne Pfeufer, Maria Grazia Pilia, Peter P Pramstaller, Bram P Prins, Olli T Raitakari, Soumya Raychaudhuri, Ken M Rice, Elizabeth J Rossin, Jerome I Rotter, Sebastian Schafer, David Schlessinger, Carsten O Schmidt, Jobanpreet Sehmi, Herman H W Silljé, Gianfranco Sinagra, Moritz F Sinner, Kamil Slowikowski, Elsayed Z Soliman, Timothy D Spector, Wilko Spiering, John A Stamatoyannopoulos, Ronald P Stolk, Konstantin Strauch, Sian-Tsung Tan, Kirill V Tarasov, Bosco Trinh, Andre G Uitterlinden, Malou van den Boogaard, Cornelia M van Duijn, Wiek H van Gilst, Jorma S Viikari, Peter M Visscher, Veronique Vitart, Uwe Völker, Melanie Waldenberger, Christian X Weichenberger, Harm-Jan Westra, Cisca Wijmenga, Bruce H Wolffenbuttel, Jian Yang, Connie R Bezzina, Patricia B Munroe, Harold Snieder, Alan F Wright, Igor Rudan, Laurie A Boyer, Folkert W Asselbergs, Dirk J van Veldhuisen, Bruno H Stricker, Bruce M Psaty, Marina Ciullo, Serena Sanna, Terho Lehtimäki, James F Wilson, Stefania Bandinelli, Alvaro Alonso, Paolo Gasparini, J Wouter Jukema, Stefan Kääb, Vilmundur Gudnason, Stephan B Felix, Susan R Heckbert, Rudolf A de Boer, Christopher Newton-Cheh, Andrew A Hicks, John C Chambers, Yalda Jamshidi, Axel Visel, Vincent M Christoffels, Aaron Isaacs, Nilesh J Samani, Paul I W de Bakker 52 Genetic Loci Influencing Myocardial Mass. J. Am. Coll. Cardiol.: 2016, 68(13);1435-48 PubMed 27659466

Xinguo Peng, Yan Lin, Jinling Li, Mengchun Liu, Jingli Wang, Xueying Li, Jingjing Liu, Xuewen Jia, Zhongcui Jing, Zuzhou Huang, Kaiqiu Chu, Shiguo Liu Evaluation of Glutathione Peroxidase 4 role in Preeclampsia. Sci Rep: 2016, 6;33300 PubMed 27641822

Nobue Yagihara, Hiroshi Watanabe, Phil Barnett, Laetitia Duboscq-Bidot, Atack C Thomas, Ping Yang, Seiko Ohno, Kanae Hasegawa, Ryozo Kuwano, Stéphanie Chatel, Richard Redon, Jean-Jacques Schott, Vincent Probst, Tamara T Koopmann, Connie R Bezzina, Arthur A M Wilde, Yukiko Nakano, Takeshi Aiba, Yoshihiro Miyamoto, Shiro Kamakura, Dawood Darbar, Brian S Donahue, Daichi Shigemizu, Toshihiro Tanaka, Tatsuhiko Tsunoda, Masayoshi Suda, Akinori Sato, Tohru Minamino, Naoto Endo, Wataru Shimizu, Minoru Horie, Dan M Roden, Naomasa Makita Variants in the SCN5A Promoter Associated With Various Arrhythmia Phenotypes. J Am Heart Assoc: 2016, 5(9); PubMed 27625342

Rangarajan D Nadadur, Michael T Broman, Bastiaan Boukens, Stefan R Mazurek, Xinan Yang, Malou van den Boogaard, Jenna Bekeny, Margaret Gadek, Tarsha Ward, Min Zhang, Yun Qiao, James F Martin, Christine E Seidman, Jon Seidman, Vincent Christoffels, Igor R Efimov, Elizabeth M McNally, Christopher R Weber, Ivan P Moskowitz Pitx2 modulates a Tbx5-dependent gene regulatory network to maintain atrial rhythm. Sci Transl Med: 2016, 8(354);354ra115 PubMed 27582060


Cardiac muscle histology
  • 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


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

Heart Development Movies


Animations showing aspects of heart development.

Week3 folding icon.jpg
 ‎‎Week 3
Page | Play
Heart1 looping icon.jpg
 ‎‎Heart Looping
Page | Play
Heart1 realign icon.jpg
 ‎‎Heart Realign
Page | Play
Heart1 atrium icon.jpg
 ‎‎Atrial Septation
Page | Play
Heart1 ventricle icon.jpg
 ‎‎Outflow Septation
Page | Play


Pages within the online Cardiac tutorial.

Heart Cartoons
Heart fields 001 icon.jpg
 ‎‎Heart Fields
Page | Play
Heart folding 002 icon.jpg
 ‎‎Primitive Heart Tube
Page | Play
Heart folding 001 icon.jpg
 ‎‎Heart Tubes
Page | Play
Heart looping 006 icon.jpg
 ‎‎Cardiac Looping
Page | Play
Heart septation 003 icon.jpg
 ‎‎Cardiac Septation
Page | Play
Heart septation 001 icon.jpg
 ‎‎Cardiac Septation
Page | Play
Outflow tract 001 icon.jpg
 ‎‎Outflow Tract
Page | Play
Page | Play
Page | Play


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
Heart historic 001 icon.jpg
Page | Play
Heart historic 002 icon.jpg
 ‎‎Week 3
Page | Play
Heart historic 003 icon.jpg
 ‎‎Week 3-5
Page | Play
Heart historic 004 icon.jpg
 ‎‎Week 4-11
Page | Play
Heart historic 005 icon.jpg
 ‎‎Embryo overview
Page | Play
Heart historic 006 icon.jpg
 ‎‎AV Septation
Page | Play
Heart historic 007 icon.jpg
 ‎‎Outflow Septation
Page | Play
Heart historic 008 icon.jpg
Page | Play
About Historic Animations
Mark Hill.jpg
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

Cardiovascular Links: Introduction | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | Heart | Coronary Circulation | Heart Valve | Heart Rate | Circulation | Blood | Blood Vessel | Blood Vessel Histology | Cardiac Muscle Histology | Lymphatic | Ductus Venosus | Spleen | Stage 22 | Abnormalities | OMIM | ECHO Meeting | Category:Cardiovascular
Historic Embryology
1912 Heart | 1912 Human Heart | 1915 Congenital Cardiac Disease | 1916 Pars Membranacea Septi | 1921 Human Brain Vascular | 1923 Head Subcutaneous Plexus | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1938 Pars Membranacea Septi | Ziegler Heart Models | Historic Disclaimer

Septation Models

Ventricular septation rotation models.

 ‎‎Ventricular Septum 1
Page | Play
 ‎‎Ventricular Septum 2
Page | Play
 ‎‎Ventricular Septum 3
Page | Play

Chicken Heart Development

Note the images of chicken heart development[4] shown below are Hamburger Hamilton Stages of chicken development, not Carnegie stages. See also Heart 3D reconstruction.

Pharyngeal Arch Arteries

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.

Embryo renal venous cartoon.jpg Adult renal venous cartoon.jpg
Embryo renal venous Adult renal venous

Links: Renal Development

Fetal Blood Flow

Fetal Blood Flow

Mean Late Fetal Blood Flows[5]

(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.
  • AAo - Ascending aorta
  • MPA - main pulmonary artery
  • DA - ductus arteriosus
  • PBF - pulmonary blood flow
  • DAo - descending aorta
  • UA - umbilical artery
  • UV - umbilical vein
  • IVC - inferior vena cava
  • SVC - superior vena cava
  • RA - right atrium
  • FO - foramen ovale
  • LA - left atrium
  • RV - right ventricle
  • LV - left ventricle
Cardiovascular Links: Fetal Blood Flow values | Mean Fetal Blood Flow | Proportions Ventricular Output | Ventricular Output (colour) | Blood Development | Cardiovascular System Development


  1. Anita Krishnan, Rajeev Samtani, Preeta Dhanantwari, Elaine Lee, Shigehito Yamada, Kohei Shiota, Mary T Donofrio, Linda Leatherbury, Cecilia W Lo A detailed comparison of mouse and human cardiac development. Pediatr. Res.: 2014; PubMed 25167202
  2. Arnold Vreeker, Leonie van Stuijvenberg, Thomas J Hund, Peter J Mohler, Peter G J Nikkels, Toon A B van Veen Assembly of the cardiac intercalated disk during pre- and postnatal development of the human heart. PLoS ONE: 2014, 9(4);e94722 PubMed 24733085 | PLoS One.
  3. Yasuo Ishii, Jonathan Langberg, Kelley Rosborough, Takashi Mikawa Endothelial cell lineages of the heart. Cell Tissue Res.: 2009, 335(1);67-73 PubMed 18682987
  4. Gert van den Berg, Antoon F M Moorman Development of the pulmonary vein and the systemic venous sinus: an interactive 3D overview. PLoS ONE: 2011, 6(7);e22055 PubMed 21779373 | PLoS One
  5. Mike Seed, Joshua F P van Amerom, Shi-Joon Yoo, Bahiyah Al Nafisi, Lars Grosse-Wortmann, Edgar Jaeggi, Michael S Jansz, Christopher K Macgowan 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: 2012, 14;79 PubMed 23181717 | J Cardiovasc Magn Reson.


Robert G Kelly The second heart field. Curr. Top. Dev. Biol.: 2012, 100;33-65 PubMed 22449840

Peter Carmeliet, Rakesh K Jain Molecular mechanisms and clinical applications of angiogenesis. Nature: 2011, 473(7347);298-307 PubMed 21593862

S Degani Fetal cerebrovascular circulation: a review of prenatal ultrasound assessment. Gynecol. Obstet. Invest.: 2008, 66(3);184-96 PubMed 18607112

M Tchirikov, H J Schröder, K Hecher Ductus venosus shunting in the fetal venous circulation: regulatory mechanisms, diagnostic methods and medical importance. Ultrasound Obstet Gynecol: 2006, 27(4);452-61 PubMed 16565980

Torvid Kiserud Physiology of the fetal circulation. Semin Fetal Neonatal Med: 2005, 10(6);493-503 PubMed 16236564

Torvid Kiserud, Ganesh Acharya The fetal circulation. Prenat. Diagn.: 2004, 24(13);1049-59 PubMed 15614842


Ronny S Jiji, Christopher M Kramer Cardiovascular magnetic resonance: applications in daily practice. Cardiol Rev: 2011, 19(5);246-54 PubMed 21808168

Domenico Ribatti, Valentin Djonov Angiogenesis in development and cancer today. Int. J. Dev. Biol.: 2011, 55(4-5);343-4 PubMed 21732277

Anthony Cammarato, Christian H Ahrens, Nakissa N Alayari, Ermir Qeli, Jasma Rucker, Mary C Reedy, Christian M Zmasek, Marjan Gucek, Robert N Cole, Jennifer E Van Eyk, Rolf Bodmer, Brian O'Rourke, Sanford I Bernstein, D Brian Foster A mighty small heart: the cardiac proteome of adult Drosophila melanogaster. PLoS ONE: 2011, 6(4);e18497 PubMed 21541028

Jeong-Ki Min, Hongryeol Park, Hyun-Jung Choi, Yonghak Kim, Bo-Jeong Pyun, Vijayendra Agrawal, Byeong-Wook Song, Jongwook Jeon, Yong-Sun Maeng, Seung-Sik Rho, Sungbo Shim, Jin-Ho Chai, Bon-Kyoung Koo, Hyo Jeong Hong, Chae-Ok Yun, Chulhee Choi, Young-Myoung Kim, Ki-Chul Hwang, Young-Guen Kwon The WNT antagonist Dickkopf2 promotes angiogenesis in rodent and human endothelial cells. J. Clin. Invest.: 2011, 121(5);1882-93 PubMed 21540552

Chaoshe Guo, Ye Sun, Bin Zhou, Rosalyn M Adam, XiaoKun Li, William T Pu, Bernice E Morrow, Anne Moon, Xue Li A Tbx1-Six1/Eya1-Fgf8 genetic pathway controls mammalian cardiovascular and craniofacial morphogenesis. J. Clin. Invest.: 2011, 121(4);1585-95 PubMed 21364285

L A Arráez-Aybar, A Turrero-Nogués, D G Marantos-Gamarra Embryonic cardiac morphometry in Carnegie stages 15-23, from the Complutense University of Madrid Institute of Embryology Human Embryo Collection. Cells Tissues Organs (Print): 2008, 187(3);211-20 PubMed 18057862

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Additional Images

See also Category:Heart ILP and Category:Heart

Ziegler Models

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Cite this page: Hill, M.A. (2016) Embryology Cardiovascular System Development. Retrieved September 29, 2016, from

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