Table 1.
Cardiac developmental milestones in the chicken according to HH stages
| HH stage | Time of incubation | Major cardiac developmental milestones |
| 1 | First few hours | Identification of cardiac progenitors54 |
| 2 | 6–7 h | Presence of precardiac cells in the epiblast lateral to the primitive streak147 |
| 3 | 12–13 h | Presence of cardiac progenitor cells of 2 distinct lineages in the anterior 2 thirds of primitive streak170 |
| 4–5 | 18–22 h | Precardiac mesoderm is specified to some degree130 |
| Cardiac precursor cells migrate to the lateral plate mesoderm (primary heart fields)84 | ||
| 6–7 | 23–26 h | The first reported markers of terminal myocardial differentiation are detected in the primary heart fields11 |
| Presumptive endocardial cells from the splanchnic mesoderm initiate the formation of the bilateral endocardial heart tubes | ||
| 8 | 26–29 h | Process of endocardial tube fusion starts to give rise to a straight heart tube160 |
| 9 | 29–33 h | Cardiac crest cells begin migrating from the neural tube's neural crest toward the aorticopulmonary septum of the outflow tract12 |
| Linear heart tube starts to loop | ||
| 10–11 | 33–45 h | Tubular heart is completely fused (except the straight portion of the outflow tract) and spontaneously beats (despite cardiac pacemaker and conduction system not being developed yet)34,46 |
| 12–13– | 45–49 h | Dextral looping phase of cardiac looping is completed90 |
| Endocardial cushions are seen as an expansion of the cardiac jelly, preceding the cushion mesenchyme92 | ||
| 13 | 50–52 h | Transformation of the c-shaped heart loop into an S-shaped heart loop90 |
| 14–15 | 50–55 h | Atrioventricular ring has formed (part of the central conduction system)19 |
| Emergence of the proepicardial organ as villous projections from the surface of the sinus venosus that gives rise to the epicardium (which eventually becomes coronary arteries and subepicardial mesenchyme)116 | ||
| 16 | 51–56 h | Atria begin to form as lateral expansions of the primitive atrial region90 |
| Both the atrioventricular and outflow tract cushions emerge92 | ||
| Trabeculation begins in the inner myocardial layers at the level of the greater curvature58 | ||
| 17–18 | 52–69 h | S-shaped heart loop is completed90 |
| The primary atrial septum begins to form91 | ||
| Villous projections of the proepicardial organ reach the dorsal wall of the heart, and the epicardium begins to cover the heart116 | ||
| 19–20 | 68–72 h | Epicardium has moved over the inner curvature of the heart116 |
| Dorsal and ventral cushions of the atrioventricular canal have started to form29 | ||
| 21–23 | 3.5–4 d | Cardiac neural crest cells have reached the outflow tract164 |
| Epicardial cells enter the myocardium for the first time89 | ||
| Leaflet formation in the atrioventricular cushion begins145 | ||
| Trabecular bundles at the level of the ventricular groove are seen (although a true interventricular septum is not present)9 | ||
| 24 | 4 d | Interatrial septum fuses with the dorsal and ventral cushions, and develops numerous secondary communications (allowing shunting of blood)99 |
| Late phase of cardiac looping (septation) begins90 | ||
| 25–26 | 4.5–5 d | Aorticopulmonary septum begins to divide the aortic and pulmonary sides of the aortic sac164 |
| Coronary vasculature begins to develop163 | ||
| 27 | 5 d | Formation of the epicardium is completed89 |
| Thickening of the compact myocardium, and trabeculation of the atrial myocardium131 | ||
| 28 | 5.5 d | Sinoatrial and atrioventricular nodes and the upper part of the atrioventricular bundle start to form3,114 |
| Atrioventricular valves start to form21,173 | ||
| 29 | 6 d | Distinct mitral and tricuspid valve primordia are present85 |
| Interventricular septum has grown toward, and fused with, the atrioventricular cushions29 | ||
| Prominent myocardial proliferation (lasting through day 8), increasing the density in the ventricular myocardial compact zone by 80%113 | ||
| 30 | 6.5 d | Formation of capillary plexi and venous sinusoids165 |
| 31 | 7 d | Septation of the distal 2/3 of the truncus is almost complete164 |
| Developing aortic and pulmonary valve leaflets are offset and angled relative to each other118 | ||
| 32–33 | 7.5–8 d | Multiple vascular channels connect the left and right aortic sinuses, and dominant channels become the left and right coronary arteries165 |
| Epicardium-derived cells are distributed throughout the heart44,89 | ||
| 34 | 8 d | Completion of the outflow tract septation by (1) the aorticopulmonary septum (distal outflow tract) and (2) the joining of the 2 proximal cushions (proximal outflow tract)71,118,164 |
| Coronary arteries are formed, and the medial and adventitial layers start to form89 | ||
| Semilunar valves are completely formed118 | ||
| Ventricular septation is complete164 | ||
| 36 | 10 d | Formation of putative conductive cells (leading to differentiation of Purkinje fibers)47,48 |
| Cardiac neural crest cells differentiate into cardiac ganglion cells156 | ||
| Atrioventricular valves are completely formed21,85 | ||
| 38 | 12 d | Coronary veins are formed, and the medial and adventitial layers begin to form |
| 40 | 14 d | Innervation by the cardiac neural crest cells is complete |
| Differentiation of medial and adventitial layers of coronary arteries and veins is complete by HH43163 | ||
| 46 | 20–21 d | Interatrial septum is closed by 2 d after hatching119 |
| Reduction of the rate of myocardial proliferation, which ceases at hatching, but increases again after hatching61 |
HH, Hamburger and Hamilton
Adapted with permission from reference 93.