Cardiovascular development Dawei Dong PHD Meg Sleeper VMD Lecture goals • Understand developmental anomalies which result in congenital heart disease. • Correlation with clinical veterinary medicine. – Common congenital heart disease in veterinary patients. Know the developmental structures that are associated with congenital heart disease. 1 Lectrue 1: Development of the Blood Cells and the Heart LEARNING GOALS 1. explain the early development of the cardiac tube from visceral mesoderm ahead of the neural plate which is then folded beneath the pharynx of the head fold. 2. outline the fusion of the cardiac tube to form the simple linear heart, the segmentation and the loop formation with sinus venosus, atrium, ventricle, bulbus cordis, truncus arteriosus. 3. define the three circulatory arcs of the heart to/from the body tissues, the yolk sac (vitelline) and the allantois (umbilical) and describe their functions 4. describe the three periods of blood cell formation related to the yolk sac, the liver and the bone marrow. 5. understand the developmental process by which the conus cordis and truncus arteriosus are adapted to give the aortic and pulmonary trunk, i.e., the heart outlet separation. 6. show how septum formation in the primitive linear heart allows separate pumping of blood into the aortic and the pulmonary trunk. 7. describe the heart inlet separation through the incorporation of the sinus venosus and the pulmonary veins into the atrium. Early development of the heart The cardiac tube folds under the gut tube…… The cardiac tube(6) is established in the early gastrula as regions of visceral mesoderm ahead of the embryo itself. As a result of the head fold, the developing heart(8) ends up beneath the pharynx. 1.Ectoderm 2.Mesoderm 3.Endoderm 4.Amniotic cavity 5.&11.Yolk sak 7.Extra-embryonic coelom 9.Allantoic bud 10.Primitive gud 12.Allantois Modified from Sadler (2006) 2 Early development of the heart ……and connects bilaterally with the dorsal aorta via the aortic arches * The heart is a U-shaped tube(2) from the cardiogenic field(1) at the anterior part of the embryo. * The dorsal aortae(3,8) form independently and then grow to meet the ventral aortae(9) in the aortic arches, while fuse caudally(6). The anterior of the cardiac tube fuses with the vitelline veins(4,5). •The sides(7) of the U-tube then fuse to produce the bulbus cordis(10), ventricle(11) and the atrium(12) as simple linear pump. 13.Pericardial cavity, 14.septum transversum, Modified from McGaedy et al (2006) 15.primitive gut, 16.brain vesicles The endoderm folds to become the gut tube and the body sides form to enclose body cavities 8 day mouse, transverse N S So N Neural tube S Somite Sp So Lateral parietal mesoderm (somatopleure) E Sp Lateral visceral mesoderm (splanchnopleure) E Gut tube 9 day mouse, transverse A Split aorta A A G Gut tube So Somatopleure, parietal mesoderm* G Sp Splanchnopleure, visceral mesoderm* So C C Cavity * Collectively a serous membrane around Sp the body cavity http://www.med.unc.edu/embryo_images/ 3 The pleuropericardial cavity divides and the cavities are lined by parietal and visceral surfaces Aorta Oesophagus Lungs Peripleural cavity Heart Pericardial cavity Parietal surface of peripleural and pericardial cavities Form a single serous membrane sac around Visceral surface of peripleural and pericardial cavities the cavity http://www.eevec.vet.ed.ac.uk/ Segmentation of the cardiac tube and loop formation At first, the sinus venosus(4) and the atrium(6) are not enclosed within the pericardium cavity(5), but because the cardiac tube outgrows the pericardial cavity, and because the tube is fixed in the pericardium at both ends, the tube becomes U-shaped with the loop of U pointing ventrally, i.e., the “bulboventricular loop”, which draws the atrium and the sinus venosus into the pericardial cavity. Continued cardiac growth results in the atrium occupying a position dorsal to the bulbus cordis(2) and the ventricle(3) and it expands toward the truncus arteriosus(1), which connects to the dorsal aortae(9) through the aortic arches(8). Modified from McGaedy et al (2006) 4 Mouse, 8 day, sagittal Mouse, 9 day, frontal Mouse, 10 day, frontal The heart twists so that the atrium is rostral to the ventricle and the bulbus cordis Mouse, 8 day, frontal The heart folds under the pharynx Mouse, 9 day, side http://www.med.unc.edu/embryo_images/ Developing vascular system Dorsal aorta Cardinal veins Mesonephros Aortic arches Vitelline vein Vitelline artery Allantoic artery Allantoic vein placenta Deoxygenated blood Mixed blood Oxygenated blood Yolk sac http://www.eevec.vet.ed.ac.uk 5 Developing vascular system THREE CIRCULATORY ARCS OF THE EMBRYONIC BLOOD SUPPLY 1. BODY CIRCULATION TRANSPORT OF O2 /FOOD MATERIALS TO TISSUES TRANSPORT OF WASTE MATERIALS AWAY 2. VITELLINE CIRCULATION CARRIES MOBILISED FOOD MATERIALS FROM THE YOLK SAC LOST FUNCTION IN MAMMALS BECAUSE SAC EMPTY CARRIES FIRST BLOOD CELLS FROM YOLK SAC WALL 3. ALLANTOIC CIRCULATION IN MAMMALS TAKES OVER THE FUNCTIONS OF THE VITELLINE ARC IN BIRDS SUPPLIES FOOD MATERIALS FROM MATERNAL CIRCULATION RETAINS AVIAN FUNCTION OF REMOVAL OF WASTE AND GAS EXCHANGE Developing vascular system THREE OVERLAPPING PERIODS OF BLOOD CELL FORMATION 1. MESOBLASTIC PERIOD FIRST BLOOD CELLS, 4MM EMBRYOS FORMED IN YOLK-SAC WALL 2. HEPATO-LIENAL PERIOD 10MM EMBRYOS FORMED IN LIVER IN SPLEEN LATER UNTIL BIRTH 3. MEDULLARY PERIOD THE ONLY LASTING ONE FROM EMBROY THROUGH ADAULT LIGE FORMS IN BONE MARROW 6 Division of inlet to the heart * The right sinus horn(1,5) is incorporated into the right atrium(7), and also forms part of cranial(10) and caudal(9) vena cava. * The pulmonary veins(2,6) are incorporated into the left atrium(8). * The septum primum(3) divides the common atrium into L and R atria. * Initially the foramen primum(4) persists as an opening, but it eventually closes. * Before it closes completely, programmed cell death results in the foramen secundum(12) * A second membrane--septum secundum(11) arises from the dorsal right atrium and extends toward the septum intermedium (but does not reach the septum intermedium) * Resultant opening is the foramen Modified from Hyttel et al (2010) ovale(13). Partitioning of the heart into four chambers * The septum primum(6) divides the common atrium(1) into right(14) and left(15) atria. * Initially the foramen primum(7) persists as an opening, but it eventually closes. * Before it closes completely, programmed cell death results in the foramen secundum(13). * A second membrane--septum secundum(16)) arises from the dorsal right atrium and extends toward the septum intermedium(8) (but does not reach the septum intermedium). * Resultant opening is the foramen ovale(19). * Septum intermedium(8) grows from endorcardial cushions to divide the atrioventricular canal to left(9) and right(10). * The interventricular septum(11) grows near the interventricular sulcus(12) to divide the ventricle(2) and the bulbus cordis(3) into left(18) and right(17) ventricles. Modified from McGaedy et al (2006) 4.cranial&5.caudal vena cava,20.cavitations. 7 Division of the outlet of the heart * Septum intermedium grows from endorcardial cushions to divide the atrioventricular canal. * Interventricular septum grows from the interventricular sulcus to divide the ventricule and the bulbus cordis into left and right ventricles. * Interventrical foramen is later closed by the membranous interventrical septum (developed from the endocardial cushion, in shuch a way that both ventricles open into the conus cordis. * Conus cordis and truncus arteriosus are divided by growing pair of cushions from their walls to form aorticopulmonary septum, rotating180, so that the aortic trunk (on the right at the top) is linked down to the left ventricle and the pulmonary trunk (on the left at the top) is linked down to the right ventricle. Modified from McGaedy et al (2006) A Mouse, 12 days, section of truncus arteriosus Cushions form within the truncus arteriosus and conus cordis will fuse to form the aortico- Mouse, 10 days, frontal section pulmonary septum separating the Blood from the atrium passes aortic and pulmonary flows to the ventricle by means of a channel. The beginnings of interatrial septum formation can be seen (A) http://www.med.unc.edu/embryo_images/ 8 REFERENCES Hyttel S, Sinowatz F, Vejlsted M (2010) Domestic animal embryology. McGeady TA, Quinn PJ, Fitzpatrick ES, Ryan MT (2006) Veterinary embryology. Sadler TW (2006) Langman's medical embryology. WEB LEARNING AIDS http://www.med.unc.edu/embryo_images/ http://www.eevec.vet.ed.ac.uk/ 9.