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Early Development of Heart LEARNING OBJECTICES: Describe Vasculogenesis and Angiogenesis Discuss the formation of Endothelial tube Discuss the Carcinogenic Area Describe the formation of heart tube Discuss the further development of heart Discuss the formation of different layers of heart Discuss the division of heart tube Describe the Rotation of Heart tube Development of Cardiovascular System The cardiovascular system is first system to function in the embryo. The primordial of heart and blood vascular system appear in the middle of third week of embryonic development. The heart start to function at the beginning of fourth week External Features of Heart Internal Features of Heart Vasculogenesis and Angiogenesis Vasculogenesis means formation of blood vessels and Angiogenesis means formation of blood cells. Both the vasculogenesis and angiogenesis both occur parallel and both processes are controlled by one regulating gene factor. VEGF is a major regulator of both cell types and plays a critical role, in coordination with other signaling pathways and transcriptional regulators, in controlling the differentiation and behavior of endothelial and blood cells during early embryonic development. The formation of embryonic vascular system involves two processes: vasculogenesis and angiogenesis. Blood vessel formation (vasculogenesis) in the embryo and extraembryonic membrane during the third week: the different step of vasculogenesis are: Mesenchymal cells differentiate into endothelial cell precursor- Angioblast (vessel forming cells) which aggregate to form isolated angiogenic cell clusters, the blood islands Small cavities appear within the blood island by confluence of intercellular clefts. Angioblasts flatten to form the endothelial cells that arrange themselves around the cavities in the blood island to form endothelium These endothelium lined cavities soon fused to form the endothelial channels (vasculogenesis) ENDOTHELIUM BLOOD ISLAND From Noden and La Hunta p 211 Vessels sprout into adjacent areas by endothelia budding and fuse other vessels The first blood cells arise in the splanchnic mesoderm on the endodermal wall of the yolk sac. Cells in the outer zone of these blood islands become vascular endothelium and enclose haematopoietic stem cells. The function of haematopoiesis is transferred during foetal development from yolk sac to liver to bone marrow. Formation of Endothelial Tubes Day 17 - Blood islands form first in the extra-embryonic mesoderm Day 18 - Blood islands form next in the intra-embryonic mesoderm Day 19 - Blood islands form in the cardiogenic mesoderm and coalesce to form a pair of endothelial heart tubes Cardiogenic area The carcinogenic area first forms between cranial edge of the trilaminar germ disc and the neural plate and just lateral to the cranial end of the neural plate, on about day 19. Splanchnopleuric mesodermal cells in, adjacent to the endodermal layer will form angioblasts that form vascular cords which will begin to coalesce into the paired lateral endocardial tubes. Later these lateral endocardial tubes will fold under the embryo, fuse, and form the primitive heart tube Formation of Heart Tube The endothelial heart tubes fuse to form a single primitive heart tube with a cranial (arterial) end and a caudal (venous) end. The heart tubes are derived from the cardiogenic mesoderm situated next to the pericardial cavity, the cranial-most end of the intra-embryonic coelom. After the formation of the head fold (at 20 days) the carcinogenic mesoderm is shifted ventrally and comes to lie ventral to the primitive pharynx. Folding of Embryo Location of Cardiogenic Area At first the horseshoe-shaped cardiogenic area lies lateral and cranial to the neural tube At later stage of development, due in folding of embryo in carnio-cadual and lateral directions, the cardiogenic area changes its position and lies in front of foregut (Primitive Pharynx) Different steps of in-folding of embryo and shifting of developing heart and pericardium Development of Heart The primordium of the heart first evident at 18 days. In the cardiogenic area, splanchnic mesenchymal cells ventral to the pericardial coelom aggregates and arrange themselves side by side to form two cardiac primodium, the Angioblastic Cords. These cords canalize to form two thin walled endocardial heart tubes. As the lateral folding occurs, the endocardial tubes approach each other and fuse to form single heart tube. Fusion of heart tubes begins at the cranial end of developing heart and extends caudally. Development of Three Layers of Heart Primodium of myocardium develops from the Splanchnic mesoderm surrounding the pericardial coelom. Twenty-three days following conception, the single, simple epithelial heart tube lies within the embryo's pericardial cavity. At this time there are three cell layers present within the heart tube. Layers of Heart Inner thin layer is the thin endothelial tube, that is separated from a thick muscular tube (primodium of myocardium) by gelatinous connective tissue called as cardiac jelly. The cardiac jelly is a structure less mass of cells which contain very few nuclei. Layers of Developing Heart The endothelial tube becomes the internal endothelial lining of heart, the Endocardium, and the primodium of myocardium becomes the muscular wall of heart, the Myocardium. The visceral pericardium, or Epicardium is derived from mesothelial cells that arise from the eternal surface of sinus venosus Division of Heart Tube As folding of head region of embryo occurs, the heart and pericardial cavity come to lie ventral to the foregut and caudal to the oropharyngeal membrane. At the same time the tubular heart elongates and develops alternate constrictions and dilatations, the trunsus arteriosus, bulbus cordis, ventricle, atrium and sinus venosus. Division of Heart Tube • With folding of the head region, the heart and pericardial cavity come to lie ventral to the foregut and caudal to the oropharyngeal membrane. At the same time, the tubular heart elongates and develops alternate constrictions and dilatations, the truncus arteriosus, bulbus cordis, ventricle, atrium and sinus venosus. . The Truncus Arteriosus is continuous cranially with the aortic sac from which the aortic arches arise. • The Sinus Venosus receives the umbilical, vitelline and common cardinal veins from the chorion, yolk sac and embryo respectively. • The arterial and venous ends of the heart are fixed by the pharyngeal arches and septum transverum respectively Rotation of different Parts of Heart . The bulbus cordis and ventricle grow faster causing the heart to bend on itself forming U-shaped Bulbo -ventricular loop. As the primordial heart bends the atrium and sinus venosus come to lie dorsal to the truncus arteriosus , bulbus cordis and ventricle At this stage the sinus venosus has developed lateral expansion, the right and left horns of sinus venosus. As the heart develops it gradually invaginates the pericardial cavity. Initially suspended from the dorsal wall by mesentery, the dorsal mesocardium. Formation & Rotation of Heart Tube Transverse Pericardial Sinus The central part of dorsal mesocardium soon degenerates, forming a communication called as Transverse Pericardial sinus between right and left sides of the pericardial cavity. At this stage the heart is attached only at its cranial and caudal ends. Circulation Through the Primordial heart The initial contractions of heart originate in muscle, that is they are of myogenic origin. Blood enters the sinus venosus from a number of sites, including the: Embryo through common cardinal veins Placenta through the umbilical veins Yolk sac through the vitelline veins Development of Veins associated with the Heart Three paired Veins drain into tubular heart of four week embryo; Vitelline veins return poorly oxygenated blood from the yolk sac Umbilical veins carry well-oxygenated blood from chorion, the primordial placenta, only the left umbilical vein persists. Common Cardinal Veins return poorly oxygenated blood from the body of embryo REFERENCES • Langman’s embryology • KLM introduction to embryology ################################################################