The mouse cardiovascular system has been used as a model for human heart and vascular development. This page has information and images from early splanchnic mesoderm differentiating into cardiomyocytes, the cardivascular system, and a series of 3D reconstructions of heart development images between E8.5 and E14.5.
E9.5 3D reconstruction mouse heart
The reconstructions show not only the overall growth of the heart during this period, but also the differences between atrial and ventricular growth on external and internal surfaces.
The final image on this page raises the issue of how early heart chambers develop from the primary heart tube. The image data suggests that the "ballooning model", rather than the "segmental model" is a better model of development.
(More? Heart Notes)
Page Links: Introduction | E8.25 to E10 Early Cardiac | E12.5 Cardiovascular System | Cardiac Neural Crest Development | 3D Cardiac Development | 3D Heart External | 3D Heart Internal | E9.5 3D Heart | Carnegie Stages Comparison | WWW Links | References | Glossary
A recent paper has looked at development of contractile activity, in early cardiomyocytes, and and blood flow.
3 somite stage (E8.25): few small contracting cardiac myocyte groups on both sides of the heart tube. (weak and irregular contractions)
4 somite stage: contractions almost coordinated.
20 somite stage (E9.25): atrioventricular canal unidirectional blood flow. (development of endocardial cushion, coordinated contractions)
Data from: Nishii K, Shibata Y. Mode and determination of the initial contraction stage in the mouse embryo heart. Anat Embryol (Berl). 2006 Mar;211(2):95-100. (Link to Volume 211, Number 2 of Anatomy and Embryology original article)
Mouse embryo (day 12.5) cardiovascular system (lateral and dorsal views) placental vessels in the first image (on right of embryo).
Heart has contributions from neural crest between the levels of post-otic hindbrain to somite 4, with the most contribution from somite 2 level.
7 somite stage: Migration of cardiac neural crest from the neural tube begins. (level post-otic hindbrain and somite 4)
Pathways dorsolateral, medial, and between somites.
Then through peri-aortic mesenchyme (lateral to pharynx), through pharyngeal arches (3, 4, 6) into the aortic sac.
32 somite stage: Colonisation of the outflow tract mesenchyme.
Data from: Chan WY, Cheung CS, Yung KM, Copp AJ. Chan WY, Cheung CS, Yung KM, Copp AJ. Cardiac neural crest of the mouse embryo: axial level of origin, migratory pathway and cell autonomy of the splotch (Sp2H) mutant effect. Development. 2004 Jul;131(14):3367-79.
The yolk sac has an early important role in the provision of progeitor cells; before E8.0 all progenitors are found in the yolk sac, which remains enriched compared with the embryo from E9.5 to E10.5. (More? Blood Notes)
4 to 8 somite stage (E8.25 - 8.5): small numbers of erythroblasts first enter the embryo (yolk sac-derived primitive erythroblasts)
26 to 30 somite stage (E10): 40% red cells steady state
Data from: McGrath KE, Koniski AD, Malik J, Palis J. Circulation is established in a stepwise pattern in the mammalian embryo. Blood. 2003 Mar 1;101(5):1669-76.
(See also Palis J, Robertson S, Kennedy M, Wall C, Keller G. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development. 1999 Nov;126(22):5073-84.)
A study of BMP (Bmp-2, Bmp-4) and homeobox (Msx-2) expression using in situ hybridization showed a differential expression pattern in cardiac tissue.
Msx-2 and Bmp-2: atrioventricular canal myocardium, atrioventricular junctional myocardium, and in the maturing myocardium of the atrioventricular valves.
Bmp-4: (E12 to E14) outflow tract myocardium, endocardial cushion of the outflow tract ridges.
Msx-2: (E11 to E14) mesenchyme of the atrioventricular endocardial cushion.
Data from: Abdelwahid E, Rice D, Pelliniemi LJ, Jokinen E. Overlapping and differential localization of Bmp-2, Bmp-4, Msx-2 and apoptosis in the endocardial cushion and adjacent tissues of the developing mouse heart. Cell Tissue Res. 2001 Jul;305(1):67-78.
Images (used with permission) and modified text are from the excellent paper Soufan AT, Ruijter JM, van den Hoff MJ, de Boer PA, Hagoort J, Moorman AF. Three-dimensional reconstruction of gene expression patterns during cardiac development. Physiol Genomics. 2003 May 13;13(3):187-95. (Physiol Genomics paper)
In these images note:
Reconstructions of the myocardium of embryonic mouse hearts from E8.5 to 14.5, drawn at the same magnification (grid size: 500 x 500 µm).
Myocardial volume increase is shown as a curved line (y-axis in mm3). (duplicate hearts at E9.5 and 10.5)
Original Image Link: Figure 2
Reconstructions of the same heart lumens. This series clearly shows the formation of atrial (smooth walled) and ventricular (trabeculated) lumen from the outer curvature of the heart tube. (duplicate hearts at E9.5 and 10.5)
Original Image Link: Figure 5
Embryonic mouse heart E9.5 lumen showing primary heart tube (purple) and developing heart chambers (gray). The left and right ventricles (LV and RV) at front and and left and right atria (LA and RA) at back and mostly obscured.
Image supports the ballooning-heart model (chambers thought to "balloon" out of primary tube) as opposed to the segmental model (textbook model of heart development).
Original Image Link: Figure 6
Data For Carnegie Stages Comparison Graph (Species/Days) |
|
|||||||||||||||
|
Species |
Stage |
9 |
10 |
11 |
12 |
13 |
14 |
15 |
16 |
17 |
18 |
19 |
20 |
21 |
22 |
23 |
|
Days |
20 |
22 |
24 |
28 |
30 |
33 |
36 |
40 |
42 |
44 |
48 |
52 |
54 |
55 |
58 |
|
|
Mouse |
Days |
9 |
9.5 |
10 |
10.5 |
11 |
11.5 |
12 |
12.5 |
13 |
13.5 |
14 |
14.5 |
15 |
15.5 |
16 |
References
Human- O'Rahilly, Early human development and the chief source of information on staged human embryos. Eur. J. Obstet. Gynec. Reprod. Biol. 9 p273 (1979)
Mouse - Theiler, The house mouse. Springer-Verlag, NY (1972) ; The Mouse its Reproduction and Development Rugh, R. Oxford University Press, Oxford (1990)
Nishii K, Shibata Y. Mode and determination of the initial contraction stage in the mouse embryo heart. Anat Embryol (Berl). 2006 Mar;211(2):95-100.
Chan WY, Cheung CS, Yung KM, Copp AJ. Chan WY, Cheung CS, Yung KM, Copp AJ. Cardiac neural crest of the mouse embryo: axial level of origin, migratory pathway and cell autonomy of the splotch (Sp2H) mutant effect. Development. 2004 Jul;131(14):3367-79.
Soufan AT, Ruijter JM, van den Hoff MJ, de Boer PA, Hagoort J, Moorman AF. Three-dimensional reconstruction of gene expression patterns during cardiac development. Physiol Genomics. 2003 May 13;13(3):187-95.
McGrath KE, Koniski AD, Malik J, Palis J. Circulation is established in a stepwise pattern in the mammalian embryo. Blood. 2003 Mar 1;101(5):1669-76.
Abdelwahid E, Rice D, Pelliniemi LJ, Jokinen E. Overlapping and differential localization of Bmp-2, Bmp-4, Msx-2 and apoptosis in the endocardial cushion and adjacent tissues of the developing mouse heart. Cell Tissue Res. 2001 Jul;305(1):67-78.
Palis J, Robertson S, Kennedy M, Wall C, Keller G. Development of erythroid and myeloid progenitors in the yolk sac and embryo proper of the mouse. Development. 1999 Nov;126(22):5073-84.
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This page introduces the mouyse as a model system for studying cardiovascular development.
Note the early staging by somite count and the commonly used acryonym for embryonic day of development as E or ED
3D Cardiac Development images (used with permission) from Physiol Genomics. 2003 May 13;13(3):187-95. Thanks to Penny Ripka APS Permissions.
Please email Dr Mark Hill if you wish to make a comment about this current project.