Distinctive Roles of Canonical and Noncanonical Wnt Signaling in Human Embryonic Cardiomyocyte Development

Silvia Mazzotta, Carlos Neves, Rory J Bonner, Andreia S Bernardo, Kevin Docherty, Stefan Hoppler* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

85 Citations (Scopus)
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Wnt signaling is a key regulator of vertebrate heart development; however, specific roles for human cardiomyocyte development remain uncertain. Here we use human embryonic stem cells (hESCs) to analyze systematically in human cardiomyocyte development the expression of endogenous Wnt signaling components, monitor pathway activity, and dissect stage-specific requirements for canonical and noncanonical Wnt signaling mechanisms using small-molecule inhibitors. Our analysis suggests that WNT3 and WNT8A, via FZD7 and canonical signaling, regulate BRACHYURY expression and mesoderm induction; that WNT5A/5B, via ROR2 and noncanonical signaling, regulate MESP1 expression and cardiovascular development; and that later in development WNT2, WNT5A/5B, and WNT11, via FZD4 and FZD6, regulate functional cardiomyocyte differentiation via noncanonical Wnt signaling. Our findings confirm in human development previously proposed roles for canonical Wnt signaling in sequential stages of vertebrate cardiomyogenesis, and identify more precise roles for noncanonical signaling and for individual Wnt signal and Wnt receptor genes in human cardiomyocyte development.

Original languageEnglish
Pages (from-to)764-776
Number of pages13
JournalStem Cell Reports
Issue number4
Early online date15 Sept 2016
Publication statusPublished - 11 Oct 2016

Bibliographical note

Open Access funded by British Heart Foundation Under a Creative Commons license

Our thanks go to Gioia Polidori Francisco for training and discussions, Kate Watt and Yvonne Turnbull for technical and laboratory managerial support, Kadri Oras and Laura Ferguson for experimental support, Po-Lin So and Bruce Conklin (Gladstone Institutes) for providing their unpublished protocols, and Yukio Nakamura for discussion. This research is supported by the British Heart Foundation (PG/12/75/29851) and the Institute of Medical Sciences. A.S.B. was supported by the British Heart Foundation (FS/12/37/29516).


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