Lecture 3.1 - Development of the heart - early development

Blastulation (Week 1)

• No specific heart development during this stage

Gastrulation (Week 2)

• No specific heart development during this stage

Neurulation (Week 3)

• Development of the heart begins
• Splanchnic part of the mesoderm gives rise to the heart
• Endodermal cells secrete VEGF, which stimulates the splanchnic part of the mesoderm
• Splanchnic part differentiates and forms two pericardial cavities and two heart tubes

Development of the Heart (Week 3)

• The two pericardial cavities and heart tubes fuse together
• Heart tubes get pushed into the pericardial cavities
• Dorsal mesocardium gives the heart tube stability and suspends the heart
• Heart forms in the head and moves down towards the chest cavity
• Mesodermal structure gets pushed down into the chest cavity (pericardial cavity)

Heart Tube Structure

• Aortic sac (AS)
• Truncus arteriosus (TA)
• Bulbus cordis (BC)
• Primitive ventricle (PV)
• Primitive atria (PA)
• Sinus venosus (SV) - 3 inflow tracts (right and left horn, plus the veins)
• Common cardinal vein (CCV)
• Umbilical vein (UV)
• Vitelline vein (VV)

Looping of the Heart (22nd-23rd Day)

• Looping takes place, and the structures get pushed around
• PA gets pushed to the back of the heart and SV follows slightly
• Causes the atria to take final position above the ventricles
• Cells from SV migrate and form a layer around the heart - formation of visceral pericardium around the heart
• Heart starts to beat at day 22 - beating cells are from the SV
• The pacemaker of the primitive heart tube is located in the caudal portion
• Sinus venosus assumes the pacemaker's role of the embryonic heart (SA node) - located more to the caudal part of the embryo

Heart Tube Development

• Aortic sac -> ascending aorta + right brachiocephalic trunk
• Truncus arteriosus -> pulmonary trunk + ascending aorta
• Bulbus cordis -> right ventricle + outflow tracts
• Primitive ventricle -> left ventricle
• Primitive atria -> left atrium + right atrium
• Cells outside the heart (cells that form the lung buds) are used to form the tracts (pulmonary veins) going into the left atrium

Septation of the Heart (~27th Day)

• Neural crest cells migrate and form the endocardial cushions in the heart tube
• Fuse together and form a septum (septum intermedium)
• Separates into the right and left AV canals

Formation of AV Valves (Week 4)

• Neural crest cells differentiate and migrate to form a ring-like structure
• Forms the valves
• Forms the Valvular annulus which connects to the valves
• Chordae tendinae is formed in this process - used to keep valves shut
• Mitral and Tricuspid valves formed

Formation of Interatrial Septum

• Chambers and valves have been made at this point
• Septum primum is formed from tissue - doesn't touch the septum intermedium yet, and this cavity produced is known as the Ostium Primum
• Septum primum fuses with the intermedium
• Another gap forms - ostium secundum
• Another tissue known as the septum secundum forms next to the septum primum
• Foramen Ovale then forms - a form of bypassing the lungs through separation of oxygenated and deoxygenated blood (communication between right and left sides of the heart)

Formation of Interventricular Septum

• Another septum develops in the ventricles - muscular portion of interventricular septum
• Membranous portion of interventricular septum forms, which connects the muscular portion of interventricular septum to the septum intermedium

Formation of Inflow Tracts to Right Atrium

• Sinus venosus (from the side of the left horn) gets absorbed into right atrium
• All veins in left horn degenerate
• Remaining left horn becomes coronary sinus in right atrium
• CCV becomes superior vena cava on the right atrium
• VV becomes inferior vena cava on right atrium
• Umbilical vein (UV) degenerates

Formation of Outflow Tracts

• Cells migrate and form ridges (Truncal and Bulbar ridges) from neural crest cells
• The structure twists - aortico-pulmonary septum forms
• Forms pulmonary tracts and aorta
• There is a region above the BC known as the conus cordis, which later forms the semi-lunar valves
• Once the outflow tracts are formed, the dorsal mesocardium disintegrates and is taken over by the new outflow tracts - leads to formation of transverse and oblique sinus