Format

Send to

Choose Destination
Dev Biol. 2019 Feb 21. pii: S0012-1606(18)30559-1. doi: 10.1016/j.ydbio.2019.02.009. [Epub ahead of print]

The Wnt inhibitor Dkk1 is required for maintaining the normal cardiac differentiation program in Xenopus laevis.

Author information

1
Institute for Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany; International Graduate School in Molecular Medicine Ulm, Ulm University, 89081 Ulm, Germany.
2
Klinik und Poliklinik für Innere Medizin I, Klinikum Rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, 81675 Munich, Germany.
3
Institute for Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
4
Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, InfoTech Oulu, Oulu University and Biobank Borealis of Northern Finland, Oulu University Hospital, Aapistie 5, FIN-90014, University of Oulu, Finland.
5
Klinik und Poliklinik für Innere Medizin I, Klinikum Rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, 81675 Munich, Germany; DZHK (German Centre for Cardiovascular Research) - Partner Site Munich Heart Alliance, Munich, Germany.
6
Klinik und Poliklinik für Innere Medizin I, Klinikum Rechts der Isar der Technischen Universität München, Ismaninger Strasse 22, 81675 Munich, Germany; DZHK (German Centre for Cardiovascular Research) - Partner Site Munich Heart Alliance, Munich, Germany. Electronic address: amoretti@mytum.de.
7
Institute for Biochemistry and Molecular Biology, Ulm University, Albert-Einstein-Allee 11, 89081 Ulm, Germany. Electronic address: michael.kuehl@uni-ulm.de.

Abstract

Wnt proteins can activate different intracellular signaling pathways. These pathways need to be tightly regulated for proper cardiogenesis. The canonical Wnt/β-catenin inhibitor Dkk1 has been shown to be sufficient to trigger cardiogenesis in gain-of-function experiments performed in multiple model systems. Loss-of-function studies however did not reveal any fundamental function for Dkk1 during cardiogenesis. Using Xenopus laevis as a model we here show for the first time that Dkk1 is required for proper differentiation of cardiomyocytes, whereas specification of cardiomyocytes remains unaffected in absence of Dkk1. This effect is at least in part mediated through regulation of non-canonical Wnt signaling via Wnt11. In line with these observations we also found that Isl1, a critical regulator for specification of the common cardiac progenitor cell (CPC) population, acts upstream of Dkk1.

KEYWORDS:

Cardiac differentiation; dkk1; isl1

PMID:
30797757
DOI:
10.1016/j.ydbio.2019.02.009
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center