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XB-ART-55215
Genes Dev January 1, 2017; 31 (13): 1325-1338.

Id genes are essential for early heart formation.

Cunningham TJ , Yu MS , McKeithan WL , Spiering S , Carrette F , Huang CT , Bushway PJ , Tierney M , Albini S , Giacca M , Mano M , Puri PL , Sacco A , Ruiz-Lozano P , Riou JF , Umbhauer M , Duester G , Mercola M , Colas AR .


Abstract
Deciphering the fundamental mechanisms controlling cardiac specification is critical for our understanding of how heart formation is initiated during embryonic development and for applying stem cell biology to regenerative medicine and disease modeling. Using systematic and unbiased functional screening approaches, we discovered that the Id family of helix-loop-helix proteins is both necessary and sufficient to direct cardiac mesoderm formation in frog embryos and human embryonic stem cells. Mechanistically, Id proteins specify cardiac cell fate by repressing two inhibitors of cardiogenic mesoderm formation-Tcf3 and Foxa2-and activating inducers Evx1, Grrp1, and Mesp1. Most importantly, CRISPR/Cas9-mediated ablation of the entire Id (Id1-4) family in mouse embryos leads to failure of anterior cardiac progenitor specification and the development of heartless embryos. Thus, Id proteins play a central and evolutionarily conserved role during heart formation and provide a novel means to efficiently produce cardiovascular progenitors for regenerative medicine and drug discovery applications.

PubMed ID: 28794185
PMC ID: PMC5580654
Article link: Genes Dev
Grant support: [+]
Genes referenced: acta2 actc1 actn3 acvr1b atl2 bckdha bcl2l11 cbln1 cdc42 cdh11 cdh5 chd4 chka chst15 cnn3 crabp2 cxcl12 dnajc6 egr1 elavl3 eomes eppk1 evx1 fam110d fgf8 fgfbp3 foxa2 frzb2 fus gadd45g gata4 gbx2.1 gbx2.2 gemin6 grm6 gsc hand2 hcn4 hdlbp id2 id3 id4 ints5 irx5 isl1 kdr klf7 klhl22 lbr lefty lsm12 map2k4 matn1 mef2c mespb mlc1 myh11 myh6 myl1 myl2 myl7 myocd myod1 myog ncoa4 nkx2-5 nodal notch3 pecam1 pitx2 postn ppp4r4 prickle1 prpf8 rasgrp3 rgma rnf213 rras slc19a2 slc1a3 smad2 smarca5 smarcd3 snai1 sox17a sox2 sox9 srprb stk4 tagln tbx5 tbxt tcf12 tcf3 tcf4 tcn2 tgfbr3 tmem63a tnnt2 tnrc6a trim67 ube2q2 vim wdr82 zic2 zmpste24
GO keywords: heart field specification [+]

Disease Ontology terms: heart disease

Article Images: [+] show captions
References:
Bardot, 2018, Pubmed [+]


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