Development of CVS I

Systemic development (cardiogenesis) • Prenatal development of the human heart

• Begins with the formation of two

• These tubes merge to form the , also called the primitive heart tube

• Primitive heart tube loops and septates into four chambers and paired arterial trunks that form the adult heart.

2 3 Early development of the heart

4 • First major system to function in the embryo.

• Primordial heart and vascular system appear in the middle of the third week (Day 21or 22).

- The rapidly growing embryo can no longer satisfy its nutritional and oxygen requirements by diffusion alone.

- A need for an efficient method of acquiring oxygen and nutrients from the maternal blood and disposing of carbon dioxide and waste products. 5 Derived from: • Splanchnic mesoderm, which forms the primordium of the heart • Paraxial and lateral mesoderm • Pharyngeal mesoderm • Neural crest cells

6 • In the splanchnopleuric mesenchyme on either side of the neural plate, a horseshoe-shaped area develops as the cardiogenic region • Formed from cardiac myoblasts and • By day 19, an endocardial tube begins to develop in each side of this region • Tubes grow, converge and merge to form a single tube – the tubular heart by programmed cell death

7 • Cardiac progenitor cells in the epiblast, lateral to the primitive streak migrate through the streak.

• Cardiogenic region develops cranially and laterally to the neural plate

• As embryonic folding continues, the two endocardial tubes are pushed into the thoracic cavity, where they fuse together at about the 22nd day

8 • Heart develop near the head of the embryo in the cardiogenic region

• Cells in the splanchnic layer of the lateral plate mesoderm are induced by pharyngeal endoderm to form cardiac myoblasts.

• Islands form an endothelial-lined tube surrounded by myoblasts, known as the cardiogenic field; the intraembryonic cavity over it develops into the pericardial cavity.

- Appearance of paired endothelial strands— angioblastic cords. 9 • Cells destined to form cranial segments of the heart, the outflow tract, migrate first, followed by right , left ventricle, and

• The two tubes migrate and form a single primitive heart tube which forms five regions: , , primitive , and sinus venosus

10 Transverse section to show the position of the blood islands in the splanchnic mesoderm layer. Cephalocaudal section showing the position of the pericardial cavity and cardiogenic field. 11 Position of the heart showing blood islands, pericardial cavity and heart tube 12 • Cords canalize to form two thin heart tubes.

• As lateral embryonic folding occurs, the endocardial heart tubes approach each other and fuse to form a single heart tube.

• Fusion of the heart tubes begins at the cranial end of the developing heart and extends caudally.

• Other blood islands appear forming a pair of longitudinal vessels, the dorsal aortae.

13 Early Development • Heart derives from embryonic mesodermal germ-layer that differentiates after gastrulation into mesothelium, endothelium and myocardium.

• Mesothelial forms the outer lining of the heart

• The inner lining of the heart, blood vessels and lymphatics develop from the endothelium

• External layer of the heart tube—the myocardium—is formed from splanchnic mesoderm surrounding the pericardial cavity. 14 • Cardiac jelly (gelatinous connective tissue) separates the thin endothelial tube from a thick myocardium. • Heart tube consists of three layers: endothelial tube becomes the internal endothelial lining of the heart— - Primordial myocardium becomes the muscular wall of the heart - myocardium - Visceral pericardium or epicardium is derived from mesothelial cells in the sinus venosus and spread over the myocardium. q Forms the coronary arteries, including their endothelial lining and smooth muscle. 15 • Homeobox transcription factor (Pitx2c) is expressed in the left heart forming field and plays an important role in the left-right patterning of the heart tube during formation of the cardiac loop.

• As folding of the head region occurs, the heart and pericardial cavity come to lie ventral to the foregut and caudal to the oropharyngeal membrane.

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