Cardiovascular Embryology Notes

THE DEVELOPMENT OF THE HEART-mesodermal derivative

CONGENITAL CARDIOVASCULAR DISEASE

-Account for 20% of the birth defects

-teratogens: lithium/alcohol/retinoic acid/maternal diseases (diabetes)

Common genetic causes:

a) Specification: Formation of cardiac crescent

-cardiac progenitor cells are derived from intraembryonic mesoderm emerging from cranial 1/3^rd primitive streak

-the progenitor cells leave the primitive streak and migrate in a cranial lateral direction to become localized on either side of the primitive streak within the splanchnic lateral plate mesoderm to form a cardiac crescent. Cells in the cardiac crescent form the primary heart field. Expression of Mesp1, Mesp2 are expressed transiently

Cell fate maps/lineage labels- fluorescent dye into cell and see where it migrates, or you can express a green fluorescent protein-this shows the cardiac crescent originates from the cranial 1/3^rd of the primitive streak

-progenitors become specified to become cardiogenic mesoderm once in the splanchnic plate mesoderm. Interaction with the endoderm is required

-The endoderm secretes various signaling molecules. Most important is Bmp 2 stimulates expression of early cardiogenic transcription factors Nkx2.5. Bmp expression occurs in most endoderm but its effects on the mesoderm are limited to cranial region of the lateral mesoderm- inhibitors are released- notochord releases chordin and noggin and neural plate/neural tube ectoderm releases Wnt1- binds to BMP and prevents signaling activity

Mutations in Nkx2.5 result in heart development defects and congenital heart malformations

-within each limb of the cardiac crescent, endocardial tubes form- vessels form by a process of vasculogenesis. Vascular endothelial growth factor derived from the cranial endoderm directs a subset of cells within the cardiac crescent into endothelial/endocardial cell lineage

Lateral endocardial tubes develop in the cardiogenic region and fuse to form the primary heart tube

-onset of contraction occurs in the left and right endocardial tubes coordinated by the pacemaker

-late in third week- cephalic and lateral folding of the embryo- brings the two lateral endocardial tubes into the thoracic region- the two endocardial tubes fuse to form a single tube- the contacting surfaces undergo programmed cell death

If there is no fusion of the two lateral endocardial tubes it leads to cardiac bifida

Four layers of the primary heart tube

-primary heart tube initially layer of endothelium

-day 22- thick mass of splanchopleuric mesoderm attaches to the endothelium and differentiates into two layers- myocardium (heart muscle) + cardiac jelly. Cardiac jelly- thick acellular matrix- hyaluronic acid and proteoglycans- secreted by myocardium and seperates myocardium from fused endocardial tubes

-on the outer surface a final layer of mesoderm surrounds the heart forming the epicardium -serous epicardium- (visceral pericardium)- formed by population of mesothelial cells that are independently derived from the splanchnopleuric mesoderm- migrate to the outside surface of heart from sinus venous

Paired dorsal aortae of the primitive circulatory system form simultaneously with the lateral endocardial tubes

-the primitive heart tube pumps before the fusion of the tubes- after fusion there is a linear heart and blood flows from the caudal end to the primitive aortas

-inflow and outflow tracts of the future heart make connection with the endocardial tubes before they are translocated to thorax and fuse to form heart

-the paired dorsal aortae develop at the same time as the lateral endocardial tubes

-paired dorsal aortae- forms the primary outflow tract of the heart- develop from the dorsal mesenchyme of the embryonic disc either side of notochord- make their connection with the endocardial tubes

-flexion + cephalic folding brings the endocardial tubes into the cervical and then thoracic- the dorsal aortae are pulled ventrally and form dorsal ventral loop- first aortic arch

-inflow of the heart- enters through the sinus venosus through the left and right sinus horns supplied by 6 vessels- 3 vessels either side of the sinus horns

The venous drainage of the embryo develops as three pairs of vessels on the left and right sides of the embryo. The vitelline veins (VV) drain the yolk sac, the cardinal veins the body (CC) and umbilical veins (UV) the developing placenta (oxygenated blood), all drain into the sinus venosus (see below).

-venous blood supply from the body of the embryo enters through pair of vessels- common cardinal veins- formed by the confluence of paired posterior cardinal veins draining the trunk and the paried anterior cardinal veins draining the head region

Constrictions and expansions subdivide the primary heart tube

-day 21- constrictions (sulci) and expansions- appear in the primitive heart tube- forms heart chambers

-inferior end/inflow end of the heart tube- the sinus venous consists of left and right sinus horns into with common cardinal veins drain

-Cranial to the sinus horns are the primitive atrium (gives rise to both left and right atrium) atrial myosin heavy chain AMCH1 is selectively expressed within the atrial cells- when excess retinoic acid added to the embryonic chicken it causes atrialisation due to the expression of AMCH1- To ensure that retinoic acid acts locally retinaldehyde dehydrogenase 2 is expressed only in the caudal part of the primitive tube

-cranial to the atrium is the ventricle (gives rise to the left ventricle)- ventricular myosin heavy chain 1 separated by atrioventricular sulcus

1) Familial hypertrophic cardiomyopathy

-autosomal dominant disease-mutation in the B-cardiac myosin heavy chain gene

thickening of ventricular walls and interventricular septum/ disorganisation of muscle fibrils-arrythmias

-the ventricle separated from the next expansion, bulbus cordis by the buloventricular sulcus/ interventricular sulcus

-inferior part of the bulbus cordis will form the inferior part of the right...

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