(Ninja Nerds) Embryology | Development of the Heart | Longer Video

Heart Development Overview

• The primary objective is to develop a single heart tube and the surrounding pericardial cavity.
• The process begins with the superior aspect (top view) of the embryo.
• The cranial aspect represents the head, while the caudal aspect represents the tail of the embryo.
• The heart initially develops in the head region, later migrating down to the thorax.

Gastrulation and Mesoderm

• During gastrulation, cells from the epiblast move through the primitive streak.
• Epiblast cells transform the hypoblast into endoderm and create a mesoderm layer between the ectoderm and endoderm.
• A cluster of mesoderm forms in the cranial region of the developing embryo, in front of the procoral plate.

Cross-Sectional View of Heart Tube Development

• Post-gastrulation, the embryo has three layers: ectoderm, mesoderm, and endoderm.
• The focus is primarily on the mesoderm layer.
• The mesoderm consists of:
  • Paraxial mesoderm (next to the notochord)
  • Intermediate mesoderm (lateral to paraxial)
  • Lateral plate mesoderm

Lateral Plate Mesoderm Layers

• The lateral plate mesoderm splits into two layers:
  • Somatic layer
  • Splanchnic layer
• The heart tube develops from the splanchnic layer of the lateral plate mesoderm.

Role of Vascular Endothelial Growth Factors (VEGF)

• Endoderm secretes vascular endothelial growth factors (VEGF) to influence the splanchnic layer.
• VEGF stimulates the differentiation and specialization of the lateral plate mesoderm.
• The mesoderm differentiates into an outer core (angioblasts) and an inner core (hemocytoblasts).
• Angioblasts form blood vessels and the heart tube.
• Hemocytoblasts develop into blood cells (red and white cells).

Heart Tube and Pericardial Cavity Formation

• Stimulated by VEGF, the lateral plate mesoderm forms heart tubes.
• Cavities develop within the lateral plate mesoderm, forming pericardial cavities.
• Through lateral folding, the edges of the embryo come together.
• The heart tubes fuse to form a single heart tube.
• The pericardial cavities merge to form a single pericardial cavity.
• The endoderm becomes the epithelial lining of the GI tract, invaginating posteriorly.

Dorsal Mesocardium and Heart Tube Layers

• The dorsal mesocardium connects the pericardial cavity to the heart tube.
• The heart tube has three layers:
  • Endocardium (inner layer): Derived from angioblasts.
  • Myocardium (outer layer): Formed from cardiac myocytes.
  • Cardiac Jelly: Myocardium secretes a jelly-like substance between the endocardium and myocardium.

Sagittal View of Heart Tube Development

• Sagittal sections help visualize the migration of the heart from the head into the thorax.
• The cardiogenic area (mesoderm that will become the heart tube) is located in the cranial region.
• Endoderm releases VEGF, stimulating the mesoderm to differentiate, forming the heart tube and pericardial cavity.
• Craniocaudal folding occurs, where the cranial and caudal ends of the embryo fold inwards.
• The folding process pulls the mesoderm (heart tube) towards the bottom (caudal) part of the embryo.
• The heart tube moves from the head to the neck and finally into the chest cavity (thorax).
• The pericardial cavity encloses the heart tube during craniocaudal folding.

Heart Tube Structure

• Blood enters from the bottom and exits from the top of the heart tube.
• The outflow tracts are the dorsal aorta.
• Key regions of the heart tube:
  • Aortic sac (top portion)
  • Truncus arteriosus
  • Bulbus cordis
  • Primitive ventricle
  • Primitive atria
  • Sinus venosus (bottom portion)
• Blood flow: Sinus venosus → Primitive atria → Primitive ventricle → Bulbus cordis → Truncus arteriosus → Dorsal aortae.

Differentiation of Heart Tube Regions

• Aortic sac leads to the dorsal aorta.
• Truncus arteriosus becomes the pulmonary artery and aorta.
• Bulbus cordis becomes the right ventricle, right, and left outflow tracts.
• Primitive ventricle becomes the left ventricle.
• Primitive atria become both the left and right atria.
• Sinus venosus has inflow tracts.
• Inflow tracts enter the sinus venosus via the right and left horns.
• Veins entering the sinus venosus:
  • Common cardinal veins
  • Umbilical veins
  • Vitelline veins

Cardiac Looping

• Cardiac looping is essential for proper heart development.
• Requires dynein proteins, and their absence can lead to Kartagener syndrome.
• Kartagener syndrome often results in dextrocardia, where the heart bends to the right instead of the left.
• During cardiac looping, the truncus arteriosus and bulbous cordis move downward and to the right.
• The primitive ventricle moves to the left of the midline.
• The primitive atria are pulled backwards and upwards.

Visceral Pericardium and Primitive Conduction System

• The sinus venosus contributes cells to the pericardial cavity.
• These cells form the visceral pericardium around the heart.
• Some sinus venosus cells infiltrate the heart, forming a primitive conduction system.
• This conduction system allows for the heart to start beating, detectable via transvaginal ultrasound around week six.

Formation of Atrioventricular (AV) Canals

• Two AV canals (right and left) need to be formed between the atria and ventricles.
• Key structures involved:
  • Truncus arteriosus
  • Bulbus cordis
  • Primitive ventricle
  • Primitive atria
  • Sinus venosus
• The atrioventricular (AV) sulcus is located between the primitive atria and the primitive ventricle.
• Neural crest cells migrate to form endocardial cushions on the anterior and posterior sides of the heart tube.
• These cushions grow and fuse to form the septum intermedium.
• The septum intermedium separates the primitive atria and primitive ventricle, forming the right and left AV canals.

Valvular Development

• Cells from the endocardial cushions form valves.
• The valves connect to form an annulus ring.
• Valve flaps and chordae tendineae develop from the annulus ring.
• The left side of the septum intermedium forms the mitral (bicuspid) valve.
• The right side of the septum intermedium forms the tricuspid valve.
• These valves create a one-way flow of blood, preventing backflow from the ventricles into the atria.

Separation of Primitive Atria

• The primitive atria need to be separated into the right and left atrium.
• A septum primum grows from the top of the primitive atria towards the septum intermedium, but does not reach it.
• The opening formed is called the ostium primum.
• The septum primum continues to grow and eventually closes the ostium primum.
• A new opening then develops towards the top of the septum primum, called the ostium secundum.
• A second septum, the septum secundum, grows to cover the ostium secundum, but does not completely close it.
• The remaining opening is called the foramen ovale.

Foramen Ovale

• The foramen ovale allows blood to bypass the lungs in utero because the fetus is in amniotic fluid and cannot breathe.
• Blood flows from the right atrium to the left atrium, then the left ventricle, and into systemic circulation without going to the lungs.
• Post-birth, the foramen ovale should close; failure to close results in a patent foramen ovale, increasing the risk of paradoxical emboli.

Ventricular Septation

• The ventricular septum divides the bulbous cordis and the primitive ventricle.
• A muscular portion of the interventricular septum grows upwards from the apex of the heart.
• A membranous portion of the interventricular septum grows downwards from the septum intermedium.
• Complete fusion of the muscular and membranous portions is necessary to close the gap.
• Failure of the membranous portion to fuse with the muscular portion can lead to a ventricular septal defect (VSD).
• This divides the bulbous cordis into the right ventricle and the primitive ventricle into the left ventricle.

Development of Venous Inflow

• The inflow tracts into the right atrium originate from the sinus venosus.
• The left and right horns of the sinus venosus receive blood from:
  • Common cardinal veins
  • Umbilical veins
  • Vitelline veins
• All veins on the left horn degenerate, leaving only the left horn itself.
• On the right horn, the umbilical vein degenerates
• The common cardinal vein and vitelline vein remain.
• The left horn shifts towards the right and partially fuses with the right horn.
• The sinus venosus is absorbed into the primitive atria.

Formation of the Coronary Sinus and Vena Cavae

• The left horn forms the coronary sinus.
• The right common cardinal vein forms the superior vena cava (SVC).
• The right vitelline vein forms the inferior vena cava (IVC).

Outflow Tract Development

• Neural crest cells are called upon to form the aortic pulmonary septum.
• Endocardial ridges or cushions form in the truncus arteriosus (truncal ridges) and bulbous cordis (bulbar ridges).
• Ridges also form that grow from anterior to posterior (conus cordis) between the truncal and bulbar ridges.
• The septum forms that create two sections that will lead to the pulmonary trunk and aortic arch.

Blood Flow Patterns

• The blood from the left ventricle flows through the posterior portion and then turns and moves through the back part of the aortic pulmonary septum.
• As it moves under the septum, it rises and exits through front portion of this aortic pulmonary septum and gives way to the aortic arch of this structure.
• On the other the bulbar septum, will have blood coming through the anterior and then the blood flow moves behind the top part of the septum to the truncal septum.
• The blood flow is going to the pulmonary trunk through the heart.

Valve Formation

• Initially, endocardial cushions form from the anterior, posterior, right, and left sides.
• Rotation and invagination lead to the splitting of the cushions.
• The posterior outflow tract becomes the aorta.
• The anterior outflow tract becomes the pulmonary trunk.
• The semilunar valves form in the outflow tracts and rotation places the Aorta toward more to the side and to the right, whereas the Pulmonary Valves lead to more the left side of the person.