Cardiac Development and Transcription Factors: Insulin Signalling, Insulin Resistance, and Intrauterine Nutritional Programming of Cardiovascular Disease

Table 1

Cardiac-specific transcription factors.

Transcription factor	Embryonic day	Dysfunction/impact/alterations	Reference
(ehand/Hand1/dHAND/HAND)	e7.5–9.5	Embryonic death in Hand1 null mice due to defects in the extraembryonic mesoderm and the yolk sac, followed by cardiac development arrest.	[11]
Mef2C	e9.5	Targeted deletion of Mef2C alters embryonic vasculature development, reduced cardiac endothelial cytokine expression, and resulted in drastic vascular anomalies and embryonic death.	[25, 26]
Tbx5	e9.5–10.5	Tbx5 null mice have unsuccessful looping of the heart and LV hypoplasia, both traits of arrested cardiac development, leading to embryonic death at e10.5.	[27]
GATA4	e10.5	Mice deficient in GATA4 displayed abnormal ventral folding, inhibition of midline fusion of the primordial heart, and endoderm defects with a wide range of lethal effects in embryos.	[28, 29]
FoxO3/FoxO4	e10.5–11	FoxO3^−/−/FoxO4^−/− embryos die due to deficient vascular and cardiac growth.	[22]
CHF1/Hey2	e13.5	CHF1/Hey2 knock-out mice displayed thinning of the myocardial wall with ectopic expression of several genes by the ventricular myocardium that are normally limited to the growing atria and trabeculae on the C57BL/6 background, with only minor anatomical changes in critical systemic arteries.	[30]
CHF1/Hey2	e15.5	Failure in CHF1/Hey2 knock-out mice to enlarge the thin layer of the myocardium and minor alterations in microvasculature formation.	[30]
FoxO1	e18.5	Transgenic expression of FoxO1 led to myocardium thickening, elevated cardiomyocyte proliferation, and reduced p21^cip1, p27^Kip1, and p57^Kip2 expression.	[31]
CHF1/Hey2	e18.5	Erratic and disordered microvasculature in knock-out mice.	[30]

HAND, heart- and neural crest derivatives-expressed protein 1; e, embryonic day; Mef2c, myocyte-specific enhancer factor 2C; FoxO1^−/−, Forkhead box protein null; Tbx5, T-box transcription factor; LV, left ventricle; CHF/Hey2, cardiovascular helix-loop-helix factor 1/Hairy/enhancer-of-split related with YRPW motif protein 2; PDGFA, platelet-derived growth factor subunit A; PDGFRA, platelet-derived growth factor receptor α; Ang1, angiotensin 1; PDGFB, platelet-derived growth factor subunit B; PDGFRB, platelet-derived growth factor receptor, beta polypeptide; VEGF, vascular endothelial growth factor; Ang2, angiotensin 2.