CARDIOVASCULAR SYSTEM

+ESTABLISHMENT OF THE CARDIOGENIC FIELD +FORMATION AND POSITION OF THE HEART TUBE +FORMATION OF THE CARDIAC LOOP +ABNORMALITIES OF CARDIAC LOOPING +MOLECULAR REGULATION OF CARDIAC DEVELOPMENT +DEVELOPMENT OF THE SINUS VENOSUS +FORMATION OF THE CARDIAC SEPTA +ENDOCARDIAL CUSHIONS AND HEART DEFECTS +SEPTUM FORMATION IN THE COMMON ATRIUM +FURTHER DIFFERENTIATION OF THE ATRIA

ESTABLISHMENT OF THE CARDIOGENIC FIELD

Dorsal view of a late presomite embryo (approximately 18 days) after removal of the amnion. Prospective myoblasts and hemangioblasts reside in the splanchnic mesoderm in front of the neural plate and on each side of the embryo.B. Transverse section through asimilar-staged embryo to show the position of the bloodislands in the splanchnic mesoderm layer. C.Cephalocaudal section through a similar-staged embryo showing the position of the pericardial cavity and cardiogenic eld. D.Scanning electron micrograph of a mouse embryo equivalent to 19 days in the human, showing coalescence of the blood islands by vasculogenesis into a horseshoe-shaped heart tube

 The vascular system appears in the middle of the third

week, when the embryo is no longer able to satisfy its nutritional requirements by diffu-sion alone. Cardiac progenitor cells lie in the epiblast,immediatelylateraltotheprimitivestreak.Fromtheret hey migrate through the streak. Cells destined to formcranial segments of the heart, the outow tract, migraterst, and cells forming more caudal portions, rightventricle, left ventricle, and sinus venosus, respectively,migrate in sequential order The cells proceed toward the cranium and position themselves rostral to the buccopharyngeal membrane and neural folds (Fig. 11.1). Here they reside in the splanchnic layer of the lateral plate mesoderm. At this time, late in the presomite stage of development, they are induced by the underlying pharyngeal endoderm to form cardiac myoblasts. Blood islands also appear in this mesoderm, where they will fom blood cells and vessels by the process of vasculogenesis

 With time, the islands unite and form a

horseshoe-shaped endothelial-lined tube surrounded by myoblasts.This region is known as the cardiogenic eld; the intraembryoniccavity over it later develops into the pericardial cavity

Formation and Position of the Heart Tube

Initially, the central portion of the cardiogenic area

is anterior to the buccopharyngeal membrane and the neural plate (Fig. 11.2 A). With closure of the neural tube and formation of the brain vesicles, however, the central nervous system grows cephalad so rapidly that it extends over the centracardiogenic area andthe future pericardial cavity (Fig. 11.2). As a result of growth of the brain andcephalic folding of the embryo, the buccopharyngeal membrane is pulled for-ward, while the heart and pericardial cavity move rst to the cervical region and nally to the thorax

Formation of the Cardiac Loop

The heart tube continues to elongate and bend

on day 23. The cephalic portion of the tube bends ventrally, caudally, and to the right (Fig. 11.6, B and C ), and the atrial (caudal) portion shifts dorso cranially and to the left (Figs. 11.6 and11.7 A). This bending, which may be due to cell shape changes, creates the cardiac loop. It is complete by day 28

Figure 11.6 Formation of the cardiac loop. A. 22 days. B. 23 days.C.24 days. Brokenline, pericardium. D and E. Scanning electron micrographs of mouse embryos showing frontal views of the process shown in the diagrams. Initially the cardiac tube is short and relatively straight (D),but as it lengthens, it bends (loops), bringing the atrial region cranial and dorsal to the ventricular region(E). The tube is organized in segments, illustrated by the different colors, from the outow region to the right ventricle to the left ventricle to the atrial region. These segments represent a craniocaudal axis that appears to be regulated by homeobox gene expression.A, primitive atrium;arrow,septum transversum;S , sinus

ABNORMALITIES OF CARDIAC LOOPING

Dextrocardia, in which the heart lies on the right

side of the thorax instead of the left, is caused because the heart loops to the left instead of the right. Dextrocardia may coincide with situs inversus,a complete reversal of asym-metry in all organs. Situs inversus, which occurs in 1/7000 individuals, usually is associated with normal physiology, although there is a slight risk of heartdefects. In other cases sidedness is random, such that some organs are re-versed and others are not; this is heterotaxy.

Molecular Regulation of Cardiac Development

Heart induction. BMPs secreted in the posterior

portion of the primitivestreak and periphery of the embryo, in combination with inhibition of WNT expression by crescent in the anterior half of the embryo, induce expression of NKX2.5 in theheart forming region of the lateral plate mesoderm (splanchnic layer).NKX2.5 is thenresponsible for heart induction.

WNT inhibitors(crescent)

NKX-2.5

BMP 2,4

Development of the Sinus Venosus

In the middle of the fourth week, the sinus venosus receives venous bloodfrom the right and left sinus horns (Fig. 11.10 A). Each horn receives blood rom three important veins: (a) the vitelline or omphalomesenteric vein,(b) the umbilical vein,and (c) the common cardinal vein. At rst communi-cation between the sinus and the atrium is wide. Soon, however, the entrance of the sinus shifts to the right (Fig. 11.10B). This shift is caused primarily by left to right shunts of blood,which occur in the venous system during the fourth and fth weeks of development

Ventral view of coronal sections through the heart at the level of the atrioventricular canal to show development of the venous valves. A. 5 weeks.B. Scanning electron micrograph of a similar-staged mouse heart showing initial formatio of the septum primum; septum spurium is not visible. Note the atrioventricular canal (arrow ).C.Fetal stage. The sinus venarum (blue) is smooth walled; it derives fromthe rightsinus horn.Arrows,blood ow.D. High magnication of the interatrial sep-tum (arrows ) of a mouse embryo at a stage similar toC.

Formation of the Cardiac Septa

Figure11.13 A andB.Septum formation by two actively growing ridges that approach each other until they fuse.C.Septum formed by a single actively growing cell mass.D, E, and F.Septum formation by merging of two expanding portions of the wall of the heart. Such a septum never completely separates two cavities.

Endocardial Cushions and Heart Defects

Because of their key location,abnormalities in

endocardial cushion formation contribute to many cardiac malformations, including atrial and ventricularseptal defects and defects involving the great vessels (i.e., transposition of the great vessels and tetralogy of Fallot).Since cells populating thec onotruncal cushions include neural crest cells and since crest cells also contribute extensively to development of the head and neck,abnormalities in these cells,produced by teratogenic agents or genetic causes, often produce both heartand craniofacial defects in the same individual.

SEPTUM FORMATION IN THE COMMON ATRIUM

Septum Formation in the Atrium.The septum primum,

asickle-shaped crest descending from the roof of the atrium, begins to divide the atrium in two but leaves a lumen,the ostiumprimum,for communication between the two sides(Fig. 11.14). Later, when the ostium primum is obliterated by fusion of the septum primum with the endocardial cushions, the ostium secundum is formed by cell death that creates an opening in the septum primum. Finally, as eptum secundum forms, but an interatrial opening, the oval foramen,persists. Only at birth, when pressure in the left atrium increases, do the two septa press against each other and close the communication between the two. Abnormal-ities in the atrial septum may vary from total

Further Differentiation of the Atria

While the primitive right atrium enlarges by

incorporation of the right sinus horn,the primitive left atrium is likewise expanding. Initially, a single embryonic pulmonary vein develops as an outgrowth of the posterior left atrial wall,just to the left of the septum primum (Fig. 11.15A). This vein gains connection with eins of the developing lung buds. During further development, the pulmonaryvein and its branches are incorporated into the left atrium, forming the large smoothwalled part of the adult atrium. Although initially one vein enter the left atrium, ultimately four pulmonary veins enter(Fig.11.15 B)as the branches are incorporated into the expanding atrial wall

in the fully developed heart, the original embryonic left atrium is rep-resented by little more than the trabeculated atrial appendage,while the smooth-walled part originates from the pulmonary veins (Fig. 11.15). On the right side the original embryonic right atrium becomes the trabeculated right atrial appendage containing the pectinate muscles, and the smooth-walled sinus venarum originates from the right horn of the sinus venosus.

Superior vena Interseptovalvular cava space Septumprim Septumsecundu um Septum m Pulmona Septumprimum spurium ry veins Sinusvenaru m

Right venousvalve

Cristaterminali s

Sinuatrialorifice Left venousvalv e

Prepared by: HANNAH-ISABELA H.MENDOZA