Yagel - Cardiovascular Morphogenesis

Cardiovascular Morphogenesis (Yagel02)

Primary Cardiogenesis

-Precardiogenic mesoderm in bilateral splanchnic layer of the lateral plate of mesoderm --> fuse rostraly at midline to --> crescent ==> Primary Myocardial Heart Tube

-Inner linings of the tube made of cardiac jelly & endocardial cells that connect to the endothelium of the vascular plexus

-Dual origin of endocardial cells: pericardiac mesoderm + splanchnic mesoderm derived cells

-Formation is in part directed by the endoderm of the primary gut (via BMP and FGF signals)

-Sidedness is decided right away as the primary heart tube is not symmetrical

-3 weeks GA--> heart tube beats w peristaltic contractions

Secondary Cardiogenesis & Organogenesis

-First Heart Field- splanchnic mesoderm that forms the primary heart tube

-Secondary Heart Field- newly recruited myocardium comes from this

-The dorsal (posterior) mesocardium is interrupted by a sinus (the oblique sinus- see picture), so that the myocardium that enters the heart can only gain access thru the arterial and venous poles

Arterial Pole Myocardial Recruitment

-See illustration for detail of what the splanchnic mesoderm and neural plate contribute to the heart tube…

-Neural Crest Cells- corm the neural tube; migrates thru splanchnic mesoderm of the second heart field. Prevly thought to be responsible for outflow tract xx (truncus, TOF, PS/PA, DORV, etc esp in 22q11del as it is expressed by the arterial pole (not the neural crest cell) so likely --> ng interactions bn the two). More recently, focus is on epigenetic bn KLF2, TGFb1 to assess cell-cell and cell-matrix interactions in the outflow tract, w role of shear stress on wall and the pharyngeal arch arteries seemingly important factors…

-e.g. Tbx1 mutation--> poor myocardial recruitment at outflow tract--> shorten and abNl remodeling of the inner curvature of myocardium-> Ao orifice not wedged bn the atria… malpositioned/DORV

-e.g. TGFb2 mutation--> abNl interaction bn pharyngeal arch mesenchyme and the endothelium--> outflow tract myocardium and endocarp cushions at the site don't induce Ao Arch formation and outflow tract septation

-e.g. Pax3 mutation--> neural crest cells are primarily abNl--> no outflow tract septation--> truncus arteriosus

-e.g. VEGF120 upregulation at subpulm outflow tract--> increase Notch and Jagged pathway expression--> short subpulm outflow tract, hyperplastic outflow tract cushions--> PS ==> TOF

-Epigenetics- hyperglycemia --> ably in second heart field mesenchyme & neural crest cells

Venous Pole Cardiac Cell Recruitment

-atria grow and incorp sinus venous myocardium dorsally

-…

Neural Crest Cells

-At the inflow tract they are 'less conspicuous' than the outflow tract

-help dvp the symp/parasymp innervation

-form a marked ring around the "pulm venous anlage"

-surround the dvping AV conduction system, then apoptose (?so maybe they induce the AV conduction system formation…)

Epicardium

-derive from posterior heart field & its covering coelomic wall mesothelium (?)

-EMT- epithelial to mesenchymal transformation --> differentiate into sinus venous myocardium, and form the epithelial structure of the Proepicardial Organ (in birds)

-migrate over the naked myocardial heart tube, then undergo EMT to form a mesenchymal subepicardial layer from epicardium derived cells. These cells then migrate into atrial/ventric myocardium to --> interstitial fibroblasts and also go to the subendocardial position. A second wave of EMT arrives when the coronary capillary plexus remodels into an arterial and venous system, w the epicardial derived cells being the source of the sm muscle cells and periarterial fibroblasts. The epicardial derived cells are needed for myocardial compaction, forming the main coronary arteries, and forming the Purkinje network

-the epicardium derived cells also migrate thru AV sulcus to the endocarp cushions, ?fx there, maybe form the fibrous annulus