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Heart 4 STAGES

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Biological Sciences
Asish Mukhopadhyay

Heart 4 STAGES OF HEART DEVELOPMENT Cardiac Crescent Heart Tube Formation Looping of Heart Tube Septation into 4 chambers CARDIAC CRESCENT / HEART TUBE splanchnic mesoderm (anterior, ventral lateral plate) diff. into:splanchnic mesoderm - myocardial precursors endocardial - endocardial precursors  endocardial endothelium  pair of heart tubes endothelium tubes coalesce into 1 during lateral-to-ventral folding myocardium lines outside of heart tube  cardiac myocytes cardiac myocytes cardiac jelly endocardium and myocardium separated by CARDIAC JELLY CARDIAC INDUCTION – (muscle) myocardial precursors acquire cardiac fate in cardiac crescent (examined by watching for heartbeat in cell culture, Nkx2.5) Nkx2.5 fate acquired AT cardiac crescent: - inductive BMP-2 signal from anterior ENDODERM BMP-2 (lateral anterior endoderm can induce cardiogenesis in grafted posterior mesoderm) - however, BMP-2 can only induce heart formation in 2-signal model anterior regions  must be a SECOND SIGNAL that is expressed anteriorly Nkx 2.5 – not essential, but earliest marker of cardiac fate ANTERIOR-POSTERIOR PATTERNING tube is divided into A/P segments by constrictions blood flow is anteriograde (posterior  anterior) spatially-restricted expression of chamber-specific myosin retinoic acid can alter boundary  role for HOX genes? LOOPING AND L/R ASYMMETRY Heart looping coverts the A-P axis into L-R asymm. heart folds leftward (Dextrocardia  rightward fold) dextrocardia L/R patterning: SHH and Nodal – expression patterns SHH, nodal defects in either cause situs inversus, randomization nodal expressed on left normally **looping is important for ALIGNING chambers with vasculature** eHAND eHAND – TF expressed in left ventricle only thought to cause looping by promoting asymmetric proliferation of cardiac myocytes Nkx 2.5 activates eHAND txn dHAND – expressed in RV; also promotes asymmetric growth dHAND MEF2C – cofactor necessary for both eHAND and dHAND MEF2C Myocyte Differenti
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