Development of the cardiovascular system - 1 Primitive cardiovascular system. Development of the heart Institute of Histology and Embryology Doc. MUDr. Zuzana Jirsová, CSc. Histology and Embryology – B81402 Lecture – 25. 3. 2014 Note: This presentation is for use by students of the 1st Medical Faculty, Charles University in Prague – solely for study purposes EXAM QUESTIONS Development of the primitive cardiovascular system Heart development. Aortic arches and their derivatives Fetal blood circulation Development of the primitive cardiovascular system Vasculogenesis (blood islands) Angiogenesis Development of the primitive heart Primitive blood circulation: Extraembryonic circulation: vitelline and umbilical Intraembryonic circulation VASCULOGENESIS Development of the blood vessels begins from the blood islands which are formed in the extraembryonic mesoderm of the yolk sac, connecting stalk, and chorion at the beginning of the third week. FGF-2 induces differentiation of hemangioblasts, a comon precursor for vessel and blood cell formation. Surface cells of blood islands, induced by VEGF, differentiate into angioblasts – precursors of the endothelial cells, and inner cells into primitive blood cells (transitory population of hemopoietic stem cells). FGF = fibroblast growth factor, VEGF = vascular endothelial growth factor Proliferation of endothelium stimulated by VEGF leads to the sprouting of vessels – angiogenesis. Vessels in the embryo start to develop about two days later in the lateral plate mesoderm. A 19-day presomite embryo Definitive hematopoetic stem cells are derived from the mesoderm surrounding aorta, gonads and mesonephros. Hematopoetic stem cells in the wall of aorta. Imunocytochemical detection CD45; a 35-day human fetus. Scheme: Langman´s Medical Embryology, Sadler, 2004 Photomicrograph: Larsen´s Human Embryology, Schoenwolf et al., 2009 Development of the primitive heart -1 Progenitor heart cells (located in the epiblast adjacent to the cranial end of the primitive streak) migrate into the splanchnic layer of the lateral plate mesoderm (cardiogenic area), where they form a horseshoe-shaped heart field (b). Induced cells of heart field form blood islands or differentiate into cardiac myoblasts (a). b amnion a Yolk sac Blood islands (heart field) g Pericardial cavity (intraembryonic coelom) b Neural plate c f Wall of thee yolk sc Somatic mesoderm (cut edge) Ektoderm (cut edge) Blood islands Communication between extraand intraembryonic coelom A transverse section through 17-day embryo b = splanchnic mesoderm with progenitor heart cells, c = extraembryonic splanchnic Dorsal surface of the late presomite embryo (ectoderm and somatic mesoderm were removed) mesoderm, f = intraembryonic coelom, g = neural plate Scheme: Langman´s Medical Embryology, Sadler, 2004; Fig.: Human Embryology, Hamilton, Mossman, 1972 Development of the primitive heart - 2 Dorsal aorta Myocardial myoblasts Epicardium Fig. C: Day-22 Day-18 Paired endothelial tubes Blood islands unite and form paired endothelial tubes. At the end of the third week tubes fuse into the endocardial tube surrounded by myoblasts (primitive myocardium) and epicardium. Heart begins to pump blood into the first aortic arches at day 22-23. Position of the heart tube. Initially the cardiogenic area is anterior to the oropharyngeal membrane and the neural plate. Growth of the brain and cephalic folding of embryo result in the change of the heart position - ventral to the foregut (fig. C) and caudally to the oropharyngeal membrane. The developing heart tube bulges into the pericardial cavity and remains attached to the pericardium by dorsal mesocardium, which finally disappers. Primitive cardiovascular system in a 20-day embryo Extraembryonic circulation: vitelline and umbilical Intraembryonic circulation dorsal intersegmental arteries Umbilical circulation Chorion, connecting stalk oxygenated blood Vitelline circulation Wall of the yolk sac Scheme: Moore, Persaud, Before We Are Born, 1993 PRIMITIVE CIRCULATION Extraembryonic circulation VILTELLINE CIRCULATION aa. vitellinae (ventral branches of the dorsal aortae) – capillary plexus in the wall of the yolk sac – vv. vitellinae (2) - sinus venosus UMBILICAL CIRCULATION aa. umbilicales (branches of the dorsal aortae) – capillary plexus (in the chorionic villi) – v. umbilicalis (in the connecting stalk); in the embryo it branches into v. umbilicalis dextra and sinistra – sinus venosus Intraembryonic circulation Truncus arteriosus - aortic arches – dorsal aortae – capillary plexus in embryo - vv. cardinales anteriores and posteriores – vv. cardinales communes - sinus venosus PRIMITIVE CARDIOVASCULAR SYSTEM (End of the fourth week; only the vessels on the left side of the embryo are shown) x Truncus arteriosus Common cardinal veins, vitelline, and umbilical veins open into the sinus venosus (x) Scheme: Langman´s Medical Embryology, Sadler, 2004 Heart tube (day – 22) neural groove ectoderm the first aortic arch BULBUS CORDIS V pericardial cavity BC V BC VENTRICLE ATRIUM sinus venosus Scheme: ÚHIEM Bending and formation of the cardiac loop (blue arrows) Days 23-24 FRONTAL SECTION OF THE HEART of a 28-day embryo TRUNCUS ARTERIOSUS CONUS CORDIS Outflow part of ventricles Primordium of the left ventricle Primordium of the right ventricle Fig.: Hamilton, Mossman, Human Embryology, 1972 FORMATION OF THE CARDIAC SEPTA (days 27 – 37) Partitioning of the common atrium and atrioventricular canal Formation of the interventricular septum Septum formation in the truncus arteriosus and conus cordis Partitioning of the atrioventricular canal, primitive atrium, and ventricle Schemes: Hamilton, Mossman, Human Embryology, 1972 Partitioning of the atrioventricular canal Endocardial cushions develop in the dorsal and ventral walls of the atrioventricular (A-V) canal. These swellings grow toward each other and fuse dividing canal into right and left A-V canals. Partitioning of the common atrium Caudal attachment Endocardial cushion muscular SP Septum primum (SP) grows as thinofcrescentthe s. secundum shaped membrane from the dorsocranial wall part of Conus the atrium toward the endocardial cushions. Opening between the free edge of SP and endocardial cushions is call foramen primum (FP). Before the fusion of SP with the endocardial cushions, cell death produces perforations A: obliteration of the in the upper portion of SP. Coalescence of these septovalvular space perforations leads to the formation of the foramen secundum (FS). A new crescent-shaped fold, septum secundum (SS) grows from the ventrocranial wall of the atrium on the right side of SP. Partitioning of the primitive ventricle When primitive ventricles begin to expand, their medial walls become apposed and gradually merge to form muscular septum. The space above the free rim of interventricular muscular septum is called interventriculare formamen. SEPTUM FORMATION IN THE COMMON ATRIUM – OVAL FORAMEN Scheme: Moore, Persaud, Before We Are Born, 1993 Septum secundum (SS) grows from the ventrocranial wall of the atrium on the right side of SP and overlaps FS. Oval opening in the SS is called foramen ovale (FO). Remaining part of SP forms valve of the FO. Before birth FO allows most of the blood to flow from the right to left atrium Partitioning of the atrioventricular canal, primitive atrium, and ventricle Schemes: Hamilton, Mossman, Human Embryology, 1972 Caudal attachment of the s. secundum Further differentiation of the atria Primitive right atrium enlarges by incorporation of the right sinus horn. Primitive left atrium is enlarged when the pulmonary vein and its branches are incorporated into muscular atrium, forming its smooth-walled part. Membranous part ofSPthe interventricular septum is derived from the Conus part A: obliteration of the septovalvular space conus septum and inferior endocardial cushion. Partitioning of the conus cordis and truncus arteriosus is formed by fusion of opposing endocardial swellings (ridges), which twist around each other, foreshadowing the spiral course of the future septum. Aorticopulmonary septum divides truncus arteriosus into ascending aorta and pulmonary trunc. Conus septum partitions outflow tracts of the left and right ventricle Partitioning of the conus cordis and truncus arteriosus: conus and aorticopulmonale septa Position of the truncal and bulbar ridges (swellings): 1 = frontal 2 = saggital 3 = frontal conus cordis Endocardial swellings (rigdes) contain the neural crest derived cells Spiral course of the ridges (180o) Spiral form of the septum Ascending aorta Ventral aspect of the heart (A,D) Transverse section through the truncus arteriosus and conus cordis (B, E) Removed ventral wall of the heart (C,F) Schemes: Moore, Persaud, Before We Are Born, 1993 Truncus pulmonalis + outflow part of the right ventricle