Development of the heart

Septation of the atria

(Day 26) midline depression results in a crescent-shaped myocardial wedge, the septum primum (day 28) Septum primum and atrial spine (spina vestibuli) grow toward the AV canal; This establishes foramen between the atria (foramen (ostium) primum) before the foramen primum closes foramen secundum appears; - septum secundum is thick and muscular; - the edge of the septum secundum leaves an opening (foramen ovale) near the floor of the right atrium.

Fusion of cushions

2 dorsal (superior) and ventral (inferior) endocardial cushions develop around the periphery of the AV canal; - the atrioventricular septum divides the common AV canal into right and left canals (end of week 6); - the AV septum fuses with septum primum;

The secondary heart field (SHF)

Adds cardiac progenitors to the outflow (arterial) end of the primitive heart tube; much of the right ventricle is derived from the this mesoderm; - Some cells from SHF eventually come to populate all parts of heart including the left ventricle.

Lateral folding

Brings the right and left sides of the cardiac crescent together, and the two limbs of the crescent fuse in the midline in cranio-caudal direction.

Development of semilunar valves

Cushion tissue is excavated and remodeled to form two cavities (the primordia of the semilunar sinuses). These cavities and the intervening tissue serve as the primordia for these valves and valvular sinuses. Development is complete by 9 weeks.

Crista terminalis

Delimits the trabeculated right atrium from the smooth-walled sinus venarum; - it's upper part contains the SA node and posterior internodal pathway.

Left and right venous valves

Develop on either side of the orifices of the SVC and IVC and the orifice of the coronary sinus; - cranial parts join to form the septum spurium; - the left valve eventually becomes part of the septum secundum; - the right venous valve forms the valve of the inferior vena cava and the valve of the coronary sinus

The completion of ventricles septation

Development of the membranous ventricular septum occurs between weeks 5 and 8. The muscular interventricular septum fuses with the conotruncal septum and the ventricular side of the AV septum.

Septation of the ventricles

End of the 4th week: protrusion of the ventral bulboventricular sulcus into the cardiac lumen - the muscular interventricular septum. By 7 weeks, expansion of the muscular interventricular septum ceases without joining the atrioventricular septum. the myocardial ridges (trabeculae) form on the inner wall of both ventricles; - the outer cardiomyocytes form an outer compact layer of myocardium; - the ventral portion of the muscular interventricular septum is trabeculated and is called the primary ventricular fold or septum; - the smooth-walled dorsal part of the septum (the inlet septum) is close to the AV canals; - on the right wall of the muscular interventricular septum the moderator band or septomarginal trabecula is present; - this connects the muscular septum with the anterior papillary muscle attached to the right AV valve.

Development of coronary arteries

Epicardial-derived mesenchymal cells provide the progenitor cells for the coronary endothelium and smooth muscle cells. The connection of the developing coronary vasculature to the aorta occurs by invasion of the developing coronary arteries through the wall of the ascending aorta.

Cardiac bifida

Failure of the cardiac crescent limbs to fuse results in this condition.

Cardiac crescent

Forms within the splanchnic mesodermal subdivision: cranial lateral plate mesoderm on both sides of the embryo (primary heart field).

Cardiac looping Day 23

Heart tube begins to elongate; - bends toward the right side into a C-shaped structure; - continuous elongation at both poles forms an S-shaped configuration; - the bulbus cordis is displaced caudally, ventrally, and to the right; - the primitive ventricle is displaced to the left; - the primitive atrium is displaced dorsally and cranially.

Dorsal mesocardium

Initially it suspends the primitive heart tube in the developing pericardial cavity but quickly ruptures. The region of the rupture becomes the transverse pericardial sinus.

Realignment of primitive chambers

Initially the AV canal lies between the primitive left atrium and ventricle; - with the myocardialization the outflow tract is repositioned toward the left; - it comes to override the AV canal during the 5th week; - at the same time, the AV canal is being divided into right and left channels by the growth of the dorsal and ventral endocardial cushions.

Conducting system development

Initially the cardiomyocytes begin contracting asynchronously; - pacemaker activity is rapidly taken over by a cluster of cells in the sinoatrial region; - these are derived either from the right common cardinal vein or the right sinus venosus (form the distinct ovoid SA node located near the left venous valve); - cells within the AV junction adjacent to the endocardial cushion form the AV node and the bundles of His; - the main conduction pathway between the SA node and AV node runs through the crista terminalis.

Venous system remodeling

Initially venous return enters the right and left sinus horns via the common cardinal veins; - later all systemic venous blood enters the right sinus horn via the superior and inferior venae cavae; - the left sinus horn ceases to grow and is transformed into the coronary sinus and the small oblique vein of the left atrium.

Truncus arteriosus

Is connected at its cranial end to the aortic sac. The aortic sac is continuous with the first aortic arch and, eventually, with the other four aortic arches

Septation of the heart

Major events occur between days 28-37 of gestation. Two basic key processes in generating septa: • differential growth and remodeling (the muscular interventricular and interatrial septa generation); • formation of endocardial-derived and neural crest cell- derived cushion tissues.

Cushion tissues

Mesenchymal-filled bulges (in atrioventricular region) and ridges (along the length of the outflow tract) are often referred to as cushion tissues; - form by the end of the cardiac looping; - endocardial-derived mesenchyme invades the extracellular matrix, proliferates, and differentiates into connective tissue; - also invaded by neural crest cells; - these cushions form the membranous portion of the interventricular and interatrial septa, conotruncual septum, play a major role in forming the cardiac skeleton of the heart, the atrioventricular valves and semilunar valves.

Cardiac progenitor cells

Migrate in a craniallateral direction from intraembryonic mesoderm in the cranial third of the primitive streak during early gastrulation.

Establishing of the primary heart field

NKX-2.5 the Master gene for heart development when this is nonfunctional it leads to defects like ASD, VSD, and conduction problems. Activin, IGF, FGF8, and SHH promote expression of cardiac specific proteins.

Pulmonary vein

Originates as a midline structure within the caudal dorsal mesocardium (week 4); - shifts to the left and branches into right and left pulmonary branches; - these bifurcate again to produce 4 pulmonary veins; - these veins then grow toward the lungs and anastomose with veins developing within the mesoderm investing the bronchial buds; - 5th week - intussusception of the pulmonary vein into the dorsal wall of the left side of the primitive atrium occurs; - the trabeculated primitive atrium forms the left auricle.

Cardiac looping Day 28

Remodeling continues; - the outflow tract comes to lie between the two presumptive atria; - cardiac looping brings the four presumptive chambers of the future heart into their definitive spatial relationship to each other; - the sinus venosus and truncus arteriosus with aortic sac get closer to one another in a process called convergence; - the craniocaudal bending facilitates cardiac looping.

Establishing laterality

Serotonin signals Pitx2c on the left side but is supressed on the Right side. Pitx2c is expressed in the left heart forming field and is considered the master gene for left-sidedness. Works in conjunction with Nodal and FGF8.

Primitive endocardial tube:

Structure of the primary heart tube (day 21) Consists of endothelium filled with cardiac jelly (a thick layer of extracellular matrix), myocardium, and epicardium.

Origin of cardiovascular system

The cardiovascular system is derived from: paraxial and lateral plate mesoderm (splanchnic mesoderm); pharyngeal mesoderm; neural crest cells.

Septation of outflow tract

The conotruncal swellings grow inward along the length of the conotruncal segment. They fuse in the craniocaudal direction to form the conotruncal septum (aorticopulmonary septum), that completely separates the right and left ventricular outflow pathways. The conotruncal swellings run in a spiral along the walls of the outflow tract.

Cranio-caudal folding

The cranial-most portion of the cardiac crescent swings ventrally and caudally and lies ventral to foregut endoderm.

Outflow tract

The cranial-most segment, (or conotruncal segment), forms the distal outflow region for both ventricles. This segment will be further subdivided into the conus arteriosus (or conus cordis) and the truncus arteriosus. The primitive ventricle is separated from the bulbus cordis (will form much of the right ventricle) by the bulboventricular sulcus.

Development of epicardium

The progenitor of the epicardium, the proepicardial organ, consists of a special group of splanchnic mesodermal cells forming at the posterior dorsal mesocardium/septum transversum junction. These cells migrate as an epithelial sheet of cells over the entire myocardial surface. The epicardial epithelium deposits an extracellular matrix between it and myocardium.

Sinus venarum

The right side of the sinus venosus is gradually incorporated into the right dorsal wall of the developing atrium The vestigial left sinus horn (the future coronary sinus) repositions to the right; - The right auricle is functionally contractile

Inflow tract

The sinus venosus consists of the left and right sinus horns. Cranial to the sinus venosus, the next two chambers are the primitive atrium and the primitive ventricle, which are separated from one another by the atrioventricular sulcus.

Fusion of cardiac crescent limbs

Two limbs fuse to make the primitive heart tube; - the endocardial tubes develop within each limb; - cell proliferation in the primary heart field continues to add the more caudal segments of the heart; - cranial body folding brings the heart tube into the thoracic region (end of week 3).

Atrioventricular valves development

begin to form between the 5th and 8th weeks from endocardial cushion tissues; - the leaflets are freed from the myocardial wall by remodeling and erosion of the ventricular myocardial wall; - this forms ventricular outpockets beneath the valvular primordia and leaves thin strands of cells that form the chordae tendineae and papillary muscle.