Cardiovascular System - Heart Development

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Introduction

Human embryo heart (day 54 - 56)
The best place for students to start is the Heart Tutorial.


In human embryos the heart begins to beat at about 22-23 days, with blood flow beginning in the 4th week. The heart is therefore one of the earliest differentiating and functioning organs.

The heart 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.

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.

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.

Heart Links: Heart Tutorial | Detailed Cardiac Development | Heart Histology | Neural Crest | 2016 Review



Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer

Basic Heart

Basic Heart Development Timeline.jpg

Advanced Heart

Advanced Heart Development Timeline GA.jpg

Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer

Some Recent Findings

  • Review - Embryology of the Cardiac Conduction System Relevant to Arrhythmias[1] "Embryogenesis of the heart involves the complex cellular differentiation of slow-conducting primary myocardium into the rapidly conducting chamber myocardium of the adult. However, small areas of relatively undifferentiated cells remain to form components of the adult cardiac conduction system (CCS) and nodal tissues. Further investigation has revealed additional areas of nodal-like tissues outside of the established CCS. The embryologic origins of these areas are similar to those of the adult CCS. Under pathologic conditions, these areas can give rise to important clinical arrhythmias."
  • Cardiomyocyte orientation modulated by the Numb family proteins-N-cadherin axis is essential for ventricular wall morphogenesis[2] "The roles of cellular orientation during trabecular and ventricular wall morphogenesis are unknown, and so are the underlying mechanisms that regulate cellular orientation. Myocardial-specific Numb and Numblike double-knockout (MDKO) hearts display a variety of defects, including in cellular orientation, patterns of mitotic spindle orientation, trabeculation, and ventricular compaction. Furthermore, Numb- and Numblike-null cardiomyocytes exhibit cellular behaviors distinct from those of control cells during trabecular morphogenesis based on single-cell lineage tracing. We investigated how Numb regulates cellular orientation and behaviors and determined that N-cadherin levels and membrane localization are reduced in MDKO hearts. To determine how Numb regulates N-cadherin membrane localization, we generated an mCherry:Numb knockin line and found that Numb localized to diverse endocytic organelles but mainly to the recycling endosome. Consistent with this localization, cardiomyocytes in MDKO did not display defects in N-cadherin internalization but rather in postendocytic recycling to the plasma membrane. Furthermore, N-cadherin overexpression via a mosaic model partially rescued the defects in cellular orientation and trabeculation of MDKO hearts. Our study unravels a phenomenon that cardiomyocytes display spatiotemporal cellular orientation during ventricular wall morphogenesis, and its disruption leads to abnormal trabecular and ventricular wall morphogenesis."
  • Myoarchitectural disarray of hypertrophic cardiomyopathy begins pre-birth[3] "Myoarchitectural disarray - the multiscalar disorganisation of myocytes, is a recognised histopathological hallmark of adult human hypertrophic cardiomyopathy (HCM). It occurs before the establishment of left ventricular hypertrophy (LVH) but its early origins and evolution around the time of birth are unknown. Our aim is to investigate whether myoarchitectural abnormalities in HCM are present in the fetal heart. We used wild-type, heterozygous and homozygous hearts (n = 56) from a Mybpc3-targeted knock-out HCM mouse model and imaged the 3D micro-structure by high-resolution episcopic microscopy. We developed a novel structure tensor approach to extract, display and quantify myocyte orientation and its local angular uniformity by helical angle, angle of intrusion and myoarchitectural disarray index, respectively, immediately before and after birth. In wild-type, we demonstrate uniformity of orientation of cardiomyocytes with smooth transitions of helical angle transmurally both before and after birth but with traces of disarray at the septal insertion points of the right ventricle. In comparison, heterozygous mice free of LVH, and homozygous mice showed not only loss of the normal linear helical angulation transmural profiles observed in wild-type but also fewer circumferentially arranged myocytes at birth. Heterozygous and homozygous showed more disarray with a wider distribution than in wild-type before birth. In heterozygous mice, disarray was seen in the anterior, septal and inferior walls irrespective of stage, whereas in homozygous mice it extended to the whole LV circumference including the lateral wall."
  • Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve Development[4] "Although cardiac neural crest cells are required at early stages of arterial valve development, their contribution during valvular leaflet maturation remains poorly understood. Here, we show in mouse that neural crest cells from pre-otic and post-otic regions make distinct contributions to the arterial valve leaflets.... Our findings demonstrate a crucial role for Krox20 in arterial valve development and reveal that an excess of neural crest cells may be associated with bicuspid aortic valve." neural crest
More recent papers  
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More? References | Discussion Page | Journal Searches | 2019 References | 2020 References

Search term: Heart Development | Heart Embryology | Cardiac Embryology | Cardiac Development | Cardiomyocyte Development

Older papers  
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.

Textbooks

UNSW Embryology

UNSW Embryology logo

Hill, M.A. (2020). UNSW Embryology (20th ed.) Retrieved March 19, 2024, from https://embryology.med.unsw.edu.au

Cardiovascular Links: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer


Heart Tutorial | 2013 Lecture Slides

The Developing Human: Clinically Oriented Embryology

The Developing Human, 10th edn.jpg

Moore, K.L., Persaud, T.V.N. & Torchia, M.G. (2015). The developing human: clinically oriented embryology (10th ed.). Philadelphia: Saunders.

(links available to UNSW students)

Larsen's Human Embryology

Larsen's human embryology 5th ed.jpg

Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.

(links available to UNSW students)

Links: Embryology Textbooks
  • Human Embryology (2nd ed.) Larson Ch7 p151-188 Heart
  • 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
  • Human Embryology Fitzgerald and Fitzgerald Ch13-17: p77-111
Links: Embryology Textbooks

Timeline

Heart Looping Sequence (SEMs).jpg

  • 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
Human Heart Timeline
Characteristic Carnegie stage: 13 14 15 16 17 18 19 20 21 22 23
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

Link: timeline

Comparison Human and Mouse

Table from Anderson RH. Teratogenecity in the setting of cardiac development and maldevelopment. (2016)

Table 1. Comparison of Human and Murine Development  
Human Mouse
Carnegie
Stage
Post-ovulatory
Days
Size (mm)
Greatest Length
Theiler
Stage
Post-conception
Days
Size (mm)
Crown-rump
11 24 2.5 - 4.5 14 9 - 9.5 2.1
12 26 3 - 5 15 9.5 - 10.25 2.5
13 28 4 - 6 16 10.25 - 10.5 3.6
14 32 5 - 7 17 10.5 4.1
15 33 7 - 9 18 11 4.6
16 37 8 - 11 19 11.5 6 - 7
17 41 11 - 14 20 12 7
18 44 13 - 17 21 12.5 - 13 8.2
19 47.5 16 - 18 21 12.5 - 13 8.2
20 50.5 18 - 22 22 13.5 - 14 9.1
21 52 22 - 24 22 13.5 - 14 9.1
22 54 23 - 28 22 13.5 - 14 9.1
23 56.5 27 - 31 22 13.5 - 14 9.1
26 17.5 - 18 17.8

Notes: Human Embryonic Development | Carnegie Stages | Mouse Development | Theiler Stage | Post-conception Days | Carnegie Stage Comparison

Reference: Anderson RH. Teratogenecity in the setting of cardiac development and maldevelopment. (2016)

Heart Innervation

Comparison of Human, Mouse and Chicken heart innervation timeline.[6]

Heart innervation 01.jpg
  • DRG - dorsal root ganglion
  • HH - Hamburger and Hamilton stage
  • LA - left atrium
  • LV - left ventricle
  • OFT - outflow tract
  • RA - right atrium
  • RV - right ventricle
  • PEO - proepicardial organ

Week 9

Images from human heart (week 9)[7]

Movies

Cardiovascular System Development | Heart Tutorial

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


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


Heart-ventricular-septum-01.jpg
 ‎‎Ventricular Septum 1
Page | Play
Heart-ventricular-septum-02.jpg
 ‎‎Ventricular Septum 2
Page | Play
Heart-ventricular-septum-03.jpg
 ‎‎Ventricular Septum 3
Page | Play
Heart embryology video 1951.jpg
 ‎‎Heart (1951)
Page | Play
Historic Animations
Heart historic 001 icon.jpg
 ‎‎Anatomy
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
 ‎‎Valve+Overview
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: cardiovascular | Heart Tutorial | Lecture - Early Vascular | Lecture - Heart | Movies | 2016 Cardiac Review | heart | coronary circulation | heart valve | heart rate | Circulation | blood | blood vessel | blood vessel histology | heart histology | Lymphatic | ductus venosus | spleen | Stage 22 | cardiovascular abnormalities | OMIM | 2012 ECHO Meeting | Category:Cardiovascular
Historic Embryology - Cardiovascular 
1902 Vena cava inferior | 1905 Brain Blood Vessels | 1909 Cervical Veins | 1909 Dorsal aorta and umbilical veins | 1912 Heart | 1912 Human Heart | 1914 Earliest Blood-Vessels | 1915 Congenital Cardiac Disease | 1915 Dura Venous Sinuses | 1916 Blood cell origin | 1916 Pars Membranacea Septi | 1919 Lower Limb Arteries | 1921 Human Brain Vascular | 1921 Spleen | 1922 Aortic-Arch System | 1922 Pig Forelimb Arteries | 1922 Chicken Pulmonary | 1923 Head Subcutaneous Plexus | 1923 Ductus Venosus | 1925 Venous Development | 1927 Stage 11 Heart | 1928 Heart Blood Flow | 1935 Aorta | 1935 Venous valves | 1938 Pars Membranacea Septi | 1938 Foramen Ovale | 1939 Atrio-Ventricular Valves | 1940 Vena cava inferior | 1940 Early Hematopoiesis | 1941 Blood Formation | 1942 Truncus and Conus Partitioning | Ziegler Heart Models | 1951 Heart Movie | 1954 Week 9 Heart | 1957 Cranial venous system | 1959 Brain Arterial Anastomoses | Historic Embryology Papers | 2012 ECHO Meeting | 2016 Cardiac Review | Historic Disclaimer

Molecular

Human heart developmental functional networks.jpg

Human heart developmental functional networks[8]

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

Human Heart and Lung Volume
Week Heart Volume (ml) Lung Volume (ml)
10 0.6 1.6
18 4.3 10.9
30 26.6 49.3
Table data is "embryonic age" while original reference used gestational age GA (from LMP)[9]
Human Heart Developmental Stroke Volume
Week Left Stroke Volume (ml) Right Stroke Volume (ml) Cardiac Output L/R (ml/min)
10 0.02 0.01 2.39 / 1.8
18 0.32 0.30 43.46 / 46.72
32 2.07 2.67 284.71 / 365.99
Table data is "embryonic age" while original reference used gestational age GA (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).[10]


Additional Images

Historic Images

References

  1. Morris GM & Ariyaratnam JP. (2019). Embryology of the Cardiac Conduction System Relevant to Arrhythmias. Card Electrophysiol Clin , 11, 409-420. PMID: 31400866 DOI.
  2. Miao L, Li J, Li J, Lu Y, Shieh D, Mazurkiewicz JE, Barroso M, Schwarz JJ, Xin HB, Singer HA, Vincent PA, Zhong W, Radice GL, Wan LQ, Fan ZC, Huang G & Wu M. (2019). Cardiomyocyte orientation modulated by the Numb family proteins-N-cadherin axis is essential for ventricular wall morphogenesis. Proc. Natl. Acad. Sci. U.S.A. , 116, 15560-15569. PMID: 31300538 DOI.
  3. Garcia-Canadilla P, Cook AC, Mohun TJ, Oji O, Schlossarek S, Carrier L, McKenna WJ, Moon JC & Captur G. (2019). Myoarchitectural disarray of hypertrophic cardiomyopathy begins pre-birth. J. Anat. , , . PMID: 31347708 DOI.
  4. Odelin G, Faure E, Coulpier F, Di Bonito M, Bajolle F, Studer M, Avierinos JF, Charnay P, Topilko P & Zaffran S. (2018). Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve. Development , 145, . PMID: 29158447 DOI.
  5. 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.
  6. Végh AMD, Duim SN, Smits AM, Poelmann RE, Ten Harkel ADJ, DeRuiter MC, Goumans MJ & Jongbloed MRM. (2016). Part and Parcel of the Cardiac Autonomic Nerve System: Unravelling Its Cellular Building Blocks during Development. J Cardiovasc Dev Dis , 3, . PMID: 29367572 DOI.
  7. Licata RH. The human embryonic heart in the ninth week. (1954) Amer. J Anat., 94: 73-125. PMID 13124266
  8. Lage K, Møllgård K, Greenway S, Wakimoto H, Gorham JM, Workman CT, Bendsen E, Hansen NT, Rigina O, Roque FS, Wiese C, Christoffels VM, Roberts AE, Smoot LB, Pu WT, Donahoe PK, Tommerup N, Brunak S, Seidman CE, Seidman JG & Larsen LA. (2010). Dissecting spatio-temporal protein networks driving human heart development and related disorders. Mol. Syst. Biol. , 6, 381. PMID: 20571530 DOI.
  9. Peralta CF, Cavoretto P, Csapo B, Falcon O & Nicolaides KH. (2006). Lung and heart volumes by three-dimensional ultrasound in normal fetuses at 12-32 weeks' gestation. Ultrasound Obstet Gynecol , 27, 128-33. PMID: 16388511 DOI.
  10. Molina FS, Faro C, Sotiriadis A, Dagklis T & Nicolaides KH. (2008). Heart stroke volume and cardiac output by four-dimensional ultrasound in normal fetuses. Ultrasound Obstet Gynecol , 32, 181-7. PMID: 18634132 DOI.

Reviews

Végh AMD, Duim SN, Smits AM, Poelmann RE, Ten Harkel ADJ, DeRuiter MC, Goumans MJ & Jongbloed MRM. (2016). Part and Parcel of the Cardiac Autonomic Nerve System: Unravelling Its Cellular Building Blocks during Development. J Cardiovasc Dev Dis , 3, . PMID: 29367572 DOI.

Articles

Cho KH, Kim JH, Murakami G, Abe H, Rodríguez-Vázquez JF & Chai OH. (2019). Nerve distribution in myocardium including the atrial and ventricular septa in late stage human fetuses. Anat Cell Biol , 52, 48-56. PMID: 30984452 DOI.

Wu SM, Chien KR & Mummery C. (2008). Origins and fates of cardiovascular progenitor cells. Cell , 132, 537-43. PMID: 18295570 DOI.

Person AD, Klewer SE & Runyan RB. (2005). Cell biology of cardiac cushion development. Int. Rev. Cytol. , 243, 287-335. PMID: 15797462 DOI.

Matsui H, Ikeda K, Nakatani K, Sakabe M, Yamagishi T, Nakanishi T & Nakajima Y. (2005). Induction of initial cardiomyocyte alpha-actin--smooth muscle alpha-actin--in cultured avian pregastrula epiblast: a role for nodal and BMP antagonist. Dev. Dyn. , 233, 1419-29. PMID: 15977172 DOI.

Moorman A, Webb S, Brown NA, Lamers W & Anderson RH. (2003). Development of the heart: (1) formation of the cardiac chambers and arterial trunks. Heart , 89, 806-14. PMID: 12807866

Anderson RH, Webb S, Brown NA, Lamers W & Moorman A. (2003). Development of the heart: (2) Septation of the atriums and ventricles. Heart , 89, 949-58. PMID: 12860885

Brand T. (2003). Heart development: molecular insights into cardiac specification and early morphogenesis. Dev. Biol. , 258, 1-19. PMID: 12781678

Yutzey KE & Kirby ML. (2002). Wherefore heart thou? Embryonic origins of cardiogenic mesoderm. Dev. Dyn. , 223, 307-20. PMID: 11891982 DOI.

Eisenberg LM. (2002). Belief vs. scientific observation: the curious story of the precardiac mesoderm. Anat. Rec. , 266, 194-7. PMID: 11920381

Davidson AJ & Zon LI. (2000). Turning mesoderm into blood: the formation of hematopoietic stem cells during embryogenesis. Curr. Top. Dev. Biol. , 50, 45-60. PMID: 10948449


Heart - Historic References

Heart - Historic References 
Historic Disclaimer - information about historic embryology pages 
Mark Hill.jpg
Pages where the terms "Historic" (textbooks, papers, people, recommendations) appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms, interpretations and recommendations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Tandler J. The Development of the Heart. (1912) Sect. II, chapt. 18, vol. 2, in Keibel F. and Mall FP. Manual of Human Embryology II. (1912) J. B. Lippincott Company, Philadelphia., pp. 534-570.

Mall FP. On the development of the human heart. (1912) Amer. J Anat. 13: 249-298.

Abbott ME. Congenital Cardiac Disease (1915) Osler & Mccrae's Modern Medicine 6, 2nd Edition.

Frazer JE. The formation of the pars membranacea septi. (1916) J Anat. 51(1): 19-29. PMID 17103800

Waterston D. The development of the heart in man. (1917) Trans. Roy. Soc. Edin., 7(2): 258-302.

McClure CFW. and Butler EG. The development of the vena cava inferior in man. (1925) Amer. J Anat. 35(3): 331-383.

Odgers PNB. The formation of the venous valves, the foramen secundum and the septum secundum in the human heart. (1935) J. Anat., 69: 412-422. PMID 17104548

Odgers PN. The development of the pars membranacea septi in the human heart. (1938) J Anat. 72(2): 247-59. https://www.ncbi.nlm.nih.gov/pubmed/17104688 PMID 17104688]

Patten BM. Developmental defects at the foramen ovale. (1938) Am J Pathol. 14(2):135-162. PMID 19970381

Odgers PNB. The development of the atrio-ventricular valves in man. (1939) J Anat. 73: 643-57. PMID 17104787

Kramer TC. The partitioning of the truncus and conus and the formation of the membranous portion of the interventricular septum in the human heart. (1942) Amer. J Anat. 71(3): 343-370.

Terms

Heart

  • 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. (2024, March 19) Embryology Cardiovascular System - Heart Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Cardiovascular_System_-_Heart_Development

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