Heart Development Overview

• Heart development involves creating a single heart tube and surrounding it with a pericardial cavity
• The process begins with the cranial aspect of the developing embryo and moves caudally

Gastrulation and Mesoderm Formation

• During gastrulation, epiblast cells migrate through the primitive streak
• These cells transform the hypoblast into the endoderm and create a mesoderm layer
• The mesoderm gathers in the cranial region of the developing embryo
• The heart starts developing in the head region before moving to the thorax

Cross-Sectional View of Heart Tube Development

• Allows for a detailed understanding of the tissue layers involved in heart formation

Sagittal Section View of Heart Tube Development

• Good for observing the heart's movement from the head to the thorax during development

Tissue Layers Post-Gastrulation

• The three layers are ectoderm, mesoderm, and endoderm
• Mesoderm is located between the ectoderm and endoderm
• The mesoderm differentiates into paraxial, intermediate, and lateral plate mesoderm

Lateral Plate Mesoderm Differentiation

• Part of the lateral plate mesoderm splits into somatic and splanchnic layers
• The heart tube arises from the splanchnic layer of the lateral plate mesoderm

Role of Vascular Endothelial Growth Factors (VEGF)

• The endoderm secretes VEGF which influences the splanchnic layer
• VEGF stimulates the lateral plate mesoderm to differentiate into angioblasts and hemocytoblasts

Angioblasts and Hemocytoblasts

• Angioblasts form blood vessels and the heart tube
• Hemocytoblasts develop into blood cells

Formation of Heart Tubes and Pericardial Cavities

• Lateral plate mesoderm is stimulated by VEGF to form heart tubes
• Pericardial cavities develop within the lateral plate mesoderm

Lateral Folding and Fusion

• Embryo edges move closer, causing ectoderm and mesoderm layers to fuse
• This fusion combines the two heart tubes into a single heart tube
• The two pericardial cavities also merge into one

Endoderm's Role

• The endoderm forms the epithelial lining of the gastrointestinal tract
• It invaginates posteriorly during development

Dorsal Mesocardium

• It connects the pericardial cavity and the heart tube
• It stabilizes the heart tube within the pericardial cavity

Heart Tube Layers

• Endocardium: The inner layer of the heart tube, derived from angioblasts
• Myocardium: Outer layer, derived from cardiac myocytes
• Cardiac Jelly: A connective tissue substance secreted by the myocardium, located between the endocardium and myocardium

Sagittal View: Cranial Caudal Folding

• Cranial caudal folding is the process of moving the developing heart from the head to the chest
• Ectoderm and endoderm start folding, pulling the mesoderm caudally

Heart Tube Movement

• The heart moves from the head, over the face and neck, and into the thorax
• During folding the heart tube gets enclosed in the pericardial cavity

Final heart tube overview

• Hard tubes fuse during cranial caudal folding and sit within the pericardial cavity

Heart Tube Structure

• The heart tube consists of several regions including the aortic sac, truncus arteriosus, bulbous cordis, primitive ventricle, primitive atria, and sinus venosus
• Blood enters from the bottom via the sinus venosus and exits via the dorsal aorta at the top of the heart tube

Dorsal Aorta Origin

• Located at the top of the heart tube
• Develops from the aortic sac

Truncus Arteriosus

• Located below the aortic sac
• Will eventually develop into the pulmonary artery and the aorta

Bulbous Cordis

• Located below the truncus arteriosus
• It develops into the right ventricle and outflow tracts

Primitive Ventricle

• Located below the bulbous cordis
• Develops into the left ventricle

Primitive Atria

• Located below the primitive ventricle
• Develops into both the left and right atria

Sinus Venosus

• Located below the primitive atria
• Serves as the inflow tract for blood entering the heart tube

Blood Flow Through the Heart Tube

• Blood flows into the sinus venosus, moves through the primitive atria, primitive ventricle, and bulbous cordis, then expels out the dorsal aorta

Transforming Heart Tube to Adult Heart

• Additional steps such as cardiac looping are needed to modify the heart tube into the structure of an adult heart

Aortic Sac

• Top part of the heart tube
• Empties into the dorsal aorta

Truncus Arteriosus

• Becomes the pulmonary trunk and aortic arch.

Bulbous Cordis

• Becomes the right ventricle
• Also the outflow tracts from both the right and left ventricles.

Primitive Ventricle

• Develops into the left ventricle

Primitive Atria

• Develops into the left and right atria

Veins Entering the Sinus Venosus

• The common cardinal veins are on the outermost part
• Umbilical veins are in the middle
• Vitelline veins are the most inward structure

Cardiac Looping

• Dependent on dynein proteins
• Dynein absence can lead to cardianer syndrome

Cardianer Syndrome

• Can result in absent cilia and improper heart looping
• May cause dextrocardia, where the heart bends to the right instead of the left

Cardiac Looping Process

• Truncus arteriosus and bulbous cordis move downward and to the right
• The primitive ventricle moves to the left of the midline
• The primitive atria gets sucked into the back

Pericardial Cavity

• Cardiac looping occurs inside this structure

Sinus Venosus and Visceral Pericardium

• Cells within the sinus venosus move into the pericardial cavity
• This forms a layer around the heart called the visceral pericardium

Primitive Conduction System

• Some cells from the sinus venosus infiltrate the heart
• Starts to form a small early conduction system

Transvaginal Ultrasound

• Can detect the primitive conduction system around week six of gestation

The heart tube, primitive atria, ventricle, and the bulbous cordes must develop septations

• This forms chambers to separate the atria from each other

AV Canals Formation

• Neural crest cells migrate and form endocardial cushions
• Cushions grow on the posterior and anterior portions of the heart tube

Septum Intermedium

• It is formed when the endocardial cushions fuse together
• It separates the primitive atria and primitive ventricle, forming two canals

AV Canals Names/Position

• Positions separated by the septum
• Right AV canal and Left AV canal

Mitral and Tricuspid Valve Development

• The endocardial cells in the septum form valves
• They connect the valves with an annulus ring
• From the flaps come chordae tendini
• Valvular apparatus on left becomes the mitral (bicuspid) valve
• Valvular apparatus on right becomes the tricuspid valve

Valves Purpose

• Provide one-way flow to prevent backflow

Interatrial Septum Formation: Septum Primum and Ostium Primum

• A septum grows down but doesn't meet the septum intermedium
• The tissue is the Septum primum
• The space not reaching the medium is the ostium primum

Ostium Secundum

• The septum primum continues to grow until reaching the septum intermedium and closing off the osteum
• Then, another hole develops at the top of the septum primum
• This is called the ostium secundum

Septum Secundum and Foramen Ovale

• Another tissue grows (septum secundum) and blocks the ostium secundum
• The small space between secundum and osteum is called the foramen ovale
• In utero, blood bypasses the right atrium to the left reducing flow to the lungs

Patent Foramen Ovale

• Caused by the closing down of the foramen ovale
• People can develop clots that cause paradoxical embolus which leads to stroke

Interventricular Septum Formation: Muscular and Membranous Portions

• Tissue grows upward in the apex called the muscular portion of the interventricular septum
• Tissue moves downwards from the septum intermedium and is the membranous portion
• They fuse with this muscular portion
• Lack of fusion causes ventricular septal defect

Bulbous Cordis Fate

• Becomes the Right Ventricle as well as Outflow Tracts

Left Horn and Right Horn Veins

• Inflow tracts into the sinus venosus
• Left and right horn are each fed by common cardinal, umbilical, and vitelline veins
• Left and right are same name

Vein Regression and Shift

• All veins of the Left Horn break down with horn left over
• Of the Right, the umbilical degenerates
• Common Cardinal and Vitelline veins remain

Sinus Venosus Absorption

• Absorbs into the Primitive Atria
• The Primitive Atria fusion forms two special structures

Coronary Sinus Formation

• Left Horn develops into the coronary sinus

Superior Vena Cava Formation

• Right Common Cardinal vein forms the superior vena cava (SVC) in the Atria

Inferior Vena Cava Formation

• The right Vitelline vein forms the inferior vena cava (IVC) in the Atria

Neural Crest Cells

• Form the aortic pulmonary septum and are important to Ridge Formation

Truncal Ridges Formation

• Forms at the top
• Forms the Truncus Arteriosus

Bulbar Ridge Formation

• Forms at the bottom
• Forms at the Bulbus Cordis

Ridge Formation

• Anterior Ridge Formation
• Posterior Ridge Formation
• These are all approaching one another spiraling to lead to corkscrew

Final Ridge Formation

• The ridges are called septum intermedium, and fuse to then separate into aorta/pulm veins

Blood Flow

• Blood flows from left ventricle > through posterior of the Bulbar Septum ridge > Underneath of the Pulmonary Septum > Over Top via the Septum ridge

Septum Rotation

• Trunk-like rotation leads to structure and splits/creates rotation

Semilunar Valves Development: Cushion Formation

• Endocardial cushions form at the junction
• The junction is bulbs cordis and conus cordis
• Anterior, Posterior and L/R formations form at this time

Rotation during semilunar valves formation

• Rotation leading to valves that form splitting into two portions

Valve Structures After Rotation/Split

• Rotation- Split after two cushions form with two total vessels coming from these

Valve Result

• Aorta / Pulmonary semi-lunar valves in correct placement are what are formed