5-350 Lecture Notes - Lecture 17: Neural Crest, Hypoplasia, Tricuspid Valve

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Outline of Lecture 17
Heart Development
I. Early heart development: cardiac crescent and heart tube
- Only splanchnic mesoderm that migrates to the cardiac crescent become
cardiogenic (committed to a cardiac fate)
- Cardiogenesis requires BMP-2 (which induces Nkx2.5 expr) and an unidentified
factor
- Cardiac crescent gives rise to 2 lineages: endocardial and myocardial cells
- Two endocardial tubes form by vasculogenesis then fuse to form a single heart
tube
- Heart tube is composed of inner endocardium and outer myocardium with
cardiac jelly in between, and is enclosed by pericardial cavity
- A/P positional cues cause heart tube to segment into distinct regions
II. Looping of heart tube
- Heart tube folds right to left, and L/R asymmetry is induced by Shh and nodal
- Looping is regulated by eHAND, which is downstream of Nkx2.5
- Ventricular chamber growth follows looping, and is regulated by eHAND in
right ventricle and dHAND in left ventricle; MEF2C may be involved with both
- Trabeculae projects form inside ventricular area then fuse to give rise to
thickened myocardium and remodeled cardiac myocytes
- Also, epicardium forms from epicardial precursors
III. Endocardial cushions
- Endocardial cushions form at the atrioventricular canal and outflow tract
- AV cushions give rise to AV valves and OT cushions give rise to semilunar
valves
- Cushion forms from expansion of cardiac jelly in AV and OT region, then
epithelial to mesenchyme transformation of endocardial cells
- E-M transformation induced by adherons produced by myocardium in the AV
and OT regions, which triggers TGF-β3 in endocardium
IV. Partitioning of the heart
- AV cushion gives rise to septum intermedium, separate AV canal into right and
left parts; realignment positions them with right and left halves of heart
- Septa form to separate the atria and ventricles
- Neural crest cells form truncoconal ridges in outflow tract and fuse to form
spiral shaped truncoconal septum; this gives rise to aorta and pulmonary trunk
V. Congenital Heart Diseases
- Situs Inversus: reversed L/R asymmetry
- Hypoplastic ventricles: lack of expansion of ventricular chamber
- Marfan’s syndrome: underlying defect is in fibrillin-1, causes mitral and
tricuspid valve defects
- Atrial septic defect: failure of shunt between right and left atria to close
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