Id genes are essential for early heart formation
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Published version
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Author(s)
Type
Journal Article
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.
Date Issued
2017-08-09
Date Acceptance
2017-07-17
Citation
Genes and Development, 2017, 31 (13), pp.1325-1338
ISSN
0890-9369
Publisher
Cold Spring Harbor Laboratory Press
Start Page
1325
End Page
1338
Journal / Book Title
Genes and Development
Volume
31
Issue
13
Copyright Statement
© 2017 Cunningham et al.; Published by Cold Spring Harbor Laboratory Press
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
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Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000407611300004&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
Developmental Biology
Genetics & Heredity
cardiac progenitors
cardiac mesoderm specification
heartless
Id proteins
CRISPR/Cas9-mediated quadruple knockout
platform for cardiac disease modeling and drug discovery
EMBRYONIC STEM-CELLS
CARDIOVASCULAR PROGENITOR CELLS
MOUSE GASTRULATION
MYOCARDIAL-CELLS
MAMMALIAN HEART
XENOPUS-LAEVIS
MESP1
PROTEINS
WNT
MESODERM
Publication Status
Published
Date Publish Online
2017-08-09