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Wnt/beta-catenin and Bmp signals control distinct sets of transcription factors in cardiac progenitor cells

Item Type:Article
Title:Wnt/beta-catenin and Bmp signals control distinct sets of transcription factors in cardiac progenitor cells
Creators Name:Klaus, A. and Mueller, M. and Schulz, H. and Saga, Y. and Martin, J.F. and Birchmeier, W.
Abstract:Progenitor cells of the first and second heart fields depend on cardiac-specific transcription factors for their differentiation. Using conditional mutagenesis of mouse embryos, we define the hierarchy of signaling events that controls the expression of cardiac-specific transcription factors during differentiation of cardiac progenitors at embryonic day 9.0. Wnt/beta-catenin and Bmp act downstream of Notch/RBPJ at this developmental stage. Mutation of Axin2, the negative regulator of canonical Wnt signaling, enhances Wnt and Bmp4 signals and suffices to rescue the arrest of cardiac differentiation caused by loss of RBPJ. Using FACS enrichment of cardiac progenitors in RBPJ and RBPJ/Axin2 mutants, embryo cultures in the presence of the Bmp inhibitor Noggin, and by crossing a Bmp4 mutation into the RBPJ/Axin2 mutant background, we show that Wnt and Bmp4 signaling activate specific and nonoverlapping cardiac-specific genes in the cardiac progenitors: Nkx2-5, Isl1 and Baf60c are controlled by Wnt/beta-catenin, and Gata4, SRF, and Mef2c are controlled by Bmp signaling. Our study contributes to the understanding of the regulatory hierarchies of cardiac progenitor differentiation and outflow tract development and has implications for understanding and modeling heart development.
Keywords:Cardiogenesis, MesP1-cre, Mesoderm Patterning, Canonical Wnt, Progenitor Differentiation in Culture, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
ISSN:0027-8424
Publisher:National Academy of Sciences (U.S.A.)
Volume:109
Number:27
Page Range:10921-10926
Date:3 July 2012
Official Publication:https://doi.org/10.1073/pnas.1121236109
PubMed:View item in PubMed

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