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

Yanchun Guo, Tatjana Dorn, Susanne J. Kühl, Alexander Linnemann, Melanie Rothe, Astrid S. Pfister, Seppo Vainio, Karl Ludwig Laugwitz, Alessandra Moretti, Michael Kühl

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalDevelopmental Biology
Volume449
Issue number1
DOIs
StatePublished - 1 May 2019
Externally publishedYes

Keywords

  • Cardiac differentiation
  • dkk1
  • isl1

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