BMP4 triggers regulatory circuits specifying the cardiac mesoderm lineage.
Bmp4
Cardiac enhancers
Cardiac mesoderm
Differentiation
Heart
Mouse
WNT signaling
Journal
Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744
Informations de publication
Date de publication:
15 05 2023
15 05 2023
Historique:
received:
18
11
2022
accepted:
10
04
2023
medline:
24
5
2023
pubmed:
21
4
2023
entrez:
21
04
2023
Statut:
ppublish
Résumé
Cardiac lineage specification in the mouse is controlled by TGFβ and WNT signaling. From fly to fish, BMP has been identified as an indispensable heart inducer. A detailed analysis of the role of Bmp4 and its effectors Smad1/5, however, was still missing. We show that Bmp4 induces cardiac mesoderm formation in murine embryonic stem cells in vitro. Bmp4 first activates Wnt3 and upregulates Nodal. pSmad1/5 and the WNT effector Tcf3 form a complex, and together with pSmad2/3 activate mesoderm enhancers and Eomes. They then cooperate with Eomes to consolidate the expression of many mesoderm factors, including T. Eomes and T form a positive- feedback loop and open additional enhancers regulating early mesoderm genes, including the transcription factor Mesp1, establishing the cardiac mesoderm lineage. In parallel, the neural fate is suppressed. Our data confirm the pivotal role of Bmp4 in cardiac mesoderm formation in the mouse. We describe in detail the consecutive and cooperative actions of three signaling pathways, BMP, WNT and Nodal, and their effector transcription factors, during cardiac mesoderm specification.
Identifiants
pubmed: 37082965
pii: 310518
doi: 10.1242/dev.201450
pmc: PMC10233716
pii:
doi:
Substances chimiques
Transcription Factors
0
Transforming Growth Factor beta
0
Bmp4 protein, mouse
0
Bone Morphogenetic Protein 4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2023. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interests The authors declare no competing or financial interests.
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