Chapter 13 - Cardiovascular System S&B
1. Establishment and Patterning of the Primary Heart Field
Introduction
• The heart is the first organ to develop and function in the embryo, ensuring the growing
embryo can meet its metabolic and oxygenation demands.
• Development begins in week 3 when cells in the epiblast migrate to form the Primary Heart
Field (PHF), which sets the stage for cardiac differentiation and morphogenesis.
• The cardiovascular system arises from a series of coordinated events involving molecular
signaling, spatial patterning, and cellular migration.
Formation of the Primary Heart Field
1. Progenitor Cell Migration:
o Progenitor cells arise in the epiblast and migrate through the primitive streak during
gastrulation.
o These cells reach the splanchnic mesoderm and form a horseshoe-shaped cluster
called the Primary Heart Field (PHF).
2. Location of the PHF:
o Found cranial to the neural folds within the splanchnic layer of lateral plate
mesoderm.
o These cells contribute to the atria, left ventricle, and part of the right ventricle.
3. Formation of the Secondary Heart Field (SHF):
o Located in the splanchnic mesoderm adjacent to the posterior pharynx.
o Cells in the SHF contribute to:
§ The remaining part of the right ventricle.
§ The conus cordis (outflow tract of both ventricles).
§ The truncus arteriosus (roots of the great vessels).
o The SHF is also critical for lengthening the heart tube and aligning the outflow
tracts.
Patterning and Laterality
• The establishment of left-right asymmetry during early development is essential for heart
morphogenesis.
• Molecular Mechanisms of Patterning:
o Serotonin (5-HT):
§ Facilitates left-sided signaling by concentrating on the left side of the
embryo.
o Nodal and Lefty2:
, § Activated on the left side, inducing expression of PITX2, the master
regulator of left-sided organ development.
o BMP2/4 and WNT inhibitors:
§ BMP signals initiate cardiac development, while WNT inhibitors (crescent
and cerberus) suppress anti-cardiac WNT signaling.
Clinical Correlation
• Laterality defects can lead to:
o Situs inversus (complete reversal of organ placement).
o Heterotaxy syndromes (randomized organ arrangement).
o Dextrocardia (heart looping to the left instead of the right).
2. Formation of the Primary Heart Tube
Blood Island Formation and Early Vasculogenesis
• In the cardiogenic region of the splanchnic mesoderm, blood islands form around day 18.
• These blood islands:
o Differentiate into angioblasts (precursors of endothelial cells) and myoblasts
(cardiac muscle cells).
o Coalesce to form paired endocardial tubes.
Fusion of Endocardial Tubes
1. Lateral Embryonic Folding:
o During the 3rd week, lateral folding brings the paired heart tubes together at the
midline.
o Fusion begins cranially and progresses caudally, forming a single endocardial tube
by day 22.
2. Head-to-Thorax Folding:
o Cephalocaudal folding positions the heart tube ventrally within the thoracic cavity.
o This explains the initial location of the heart cranial to the oropharyngeal membrane.
Structure of the Primitive Heart Tube
The primitive heart tube is divided into five regions, cranial to caudal:
1. Truncus Arteriosus:
o Forms the proximal roots of the great arteries (aorta and pulmonary trunk).
2. Bulbus Cordis:
o Contributes to the right ventricle (proximal part).
o The midportion forms the conus cordis (outflow tracts).
o The distal portion contributes to the truncus arteriosus.
1. Establishment and Patterning of the Primary Heart Field
Introduction
• The heart is the first organ to develop and function in the embryo, ensuring the growing
embryo can meet its metabolic and oxygenation demands.
• Development begins in week 3 when cells in the epiblast migrate to form the Primary Heart
Field (PHF), which sets the stage for cardiac differentiation and morphogenesis.
• The cardiovascular system arises from a series of coordinated events involving molecular
signaling, spatial patterning, and cellular migration.
Formation of the Primary Heart Field
1. Progenitor Cell Migration:
o Progenitor cells arise in the epiblast and migrate through the primitive streak during
gastrulation.
o These cells reach the splanchnic mesoderm and form a horseshoe-shaped cluster
called the Primary Heart Field (PHF).
2. Location of the PHF:
o Found cranial to the neural folds within the splanchnic layer of lateral plate
mesoderm.
o These cells contribute to the atria, left ventricle, and part of the right ventricle.
3. Formation of the Secondary Heart Field (SHF):
o Located in the splanchnic mesoderm adjacent to the posterior pharynx.
o Cells in the SHF contribute to:
§ The remaining part of the right ventricle.
§ The conus cordis (outflow tract of both ventricles).
§ The truncus arteriosus (roots of the great vessels).
o The SHF is also critical for lengthening the heart tube and aligning the outflow
tracts.
Patterning and Laterality
• The establishment of left-right asymmetry during early development is essential for heart
morphogenesis.
• Molecular Mechanisms of Patterning:
o Serotonin (5-HT):
§ Facilitates left-sided signaling by concentrating on the left side of the
embryo.
o Nodal and Lefty2:
, § Activated on the left side, inducing expression of PITX2, the master
regulator of left-sided organ development.
o BMP2/4 and WNT inhibitors:
§ BMP signals initiate cardiac development, while WNT inhibitors (crescent
and cerberus) suppress anti-cardiac WNT signaling.
Clinical Correlation
• Laterality defects can lead to:
o Situs inversus (complete reversal of organ placement).
o Heterotaxy syndromes (randomized organ arrangement).
o Dextrocardia (heart looping to the left instead of the right).
2. Formation of the Primary Heart Tube
Blood Island Formation and Early Vasculogenesis
• In the cardiogenic region of the splanchnic mesoderm, blood islands form around day 18.
• These blood islands:
o Differentiate into angioblasts (precursors of endothelial cells) and myoblasts
(cardiac muscle cells).
o Coalesce to form paired endocardial tubes.
Fusion of Endocardial Tubes
1. Lateral Embryonic Folding:
o During the 3rd week, lateral folding brings the paired heart tubes together at the
midline.
o Fusion begins cranially and progresses caudally, forming a single endocardial tube
by day 22.
2. Head-to-Thorax Folding:
o Cephalocaudal folding positions the heart tube ventrally within the thoracic cavity.
o This explains the initial location of the heart cranial to the oropharyngeal membrane.
Structure of the Primitive Heart Tube
The primitive heart tube is divided into five regions, cranial to caudal:
1. Truncus Arteriosus:
o Forms the proximal roots of the great arteries (aorta and pulmonary trunk).
2. Bulbus Cordis:
o Contributes to the right ventricle (proximal part).
o The midportion forms the conus cordis (outflow tracts).
o The distal portion contributes to the truncus arteriosus.
