Table 1.
Gene | Loss-of-function cardiac phenotype a | Known downstream targets expressed in EPDCs |
References |
---|---|---|---|
Wt1 | Ventricular non-compaction; impaired epicardial EMT; impaired coronary plexus formation; pericardial hemorrhaging; die by E13.5 |
Itga4, Nestin, TrkB, Coronin1B, Raldh2, Snai1, Snai2 |
[11,12,37–43] |
Tbx18 | Caval vein defects; sinus horn myocardial hypoplasia; neonatal lethality |
Snai2 | [40,74,75] |
Tcf21 | Aberrant smooth muscle differentiation; loss of cardiac fibroblasts; pericardial hemorrhaging; neonatal lethality |
None identified | [8,13,57] |
Nfatc1 |
bReduced cardiac fibrous matrix with decreased coronary vessel penetration; neonatal lethality |
Ctsk | [9,87,88] |
Snai1 | b,cPhenotypically normal and viable | E-cadherin, Mmp15 | [92,93,96,97] |
Snai2 | Phenotypically normal and viable | None identified | [40] |
Sox9 | Hypoplastic endocardial cushions. Embryonic lethality at E11.5–E12 due to congestive heart failure. |
None identified | [102,104,108] |
Scleraxis | Thickened valves; viable | Col1a2 | [106,107] |
C/EBP |
dImproved cardiac function after ischemia/reperfusion injury |
Raldh2, Wt1 | [32] |
Hand2 |
eEpicardial blistering; abnormal coronary vessel development; loss of cardiac fibroblasts; persistent truncus arteriosus. Embryonic lethality by E14.5. |
Pdgfra | [101] |
Twist1 | Abnormal outflow tract endocardial cushion mesenchyme. Embryonic lethality by E11.5. |
Tbx20, Snai2 | [30,76,100] |
Described phenotypes are due to knockout mouse models, except in cases of epicardial-specific gene deletion, as indicated; Gene (floxed allele) was deleted from the
Wt1Cre,
Tbx18Cre, or
Hand1Cre lineages, as indicated;
Antisense adenoviral-mediated knockdown.