Bmp2 and Notch cooperate to pattern the embryonic endocardium

Development
Tania PapoutsiJosé Luis de la Pompa

Abstract

Signaling interactions between the myocardium and endocardium pattern embryonic cardiac regions, instructing their development to fulfill specific functions in the mature heart. We show that ectopic Bmp2 expression in the mouse chamber myocardium changes the transcriptional signature of adjacent chamber endocardial cells into valve tissue, and enables them to undergo epithelial-mesenchyme transition. This induction is independent of valve myocardium specification and requires high levels of Notch1 activity. Biochemical experiments suggest that Bmp2-mediated Notch1 induction is achieved through transcriptional activation of the Notch ligand Jag1, and physical interaction of Smad1/5 with the intracellular domain of the Notch1 receptor. Thus, widespread myocardial Bmp2 and endocardial Notch signaling drive presumptive ventricular endocardium to differentiate into valve endocardium. Understanding the molecular basis of valve development is instrumental to designing therapeutic strategies for congenital heart valve defects.

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Citations

Jul 16, 2019·Expert Opinion on Therapeutic Targets·Giorgio AquilaAnna Malaschicheva
Feb 20, 2020·Circulation Research·Felix GunawanAnabela Bensimon-Brito
Nov 9, 2018·Journal of Cardiovascular Development and Disease·Robert E Poelmann, Adriana C Gittenberger-de Groot
Oct 6, 2018·Nature Reviews. Cardiology·Donal MacGroganJosé Luis de la Pompa
Nov 7, 2019·Journal of Cardiovascular Development and Disease·Gaëlle OdelinStéphane Zaffran
Oct 13, 2020·Tissue Engineering. Part B, Reviews·Kathleen Zohorsky, Kibret Mequanint
Sep 1, 2019·Molecular & Cellular Proteomics : MCP·Rebeca Torregrosa-CarriónJosé Luis de la Pompa
Oct 27, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Laura Andrés-DelgadoNadia Mercader
May 1, 2021·Journal of Cardiovascular Development and Disease·Sonia StefanovicStéphane Zaffran
Jun 21, 2021·Current Opinion in Cell Biology·Felix GunawanDidier Y R Stainier
Jul 24, 2021·Cell Death & Disease·Belén PradosJosé Luis de la Pompa

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