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

Lookup NU author(s): Dr Silvia Mazzotta

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

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.

Publication metadata

Author(s): Mazzotta S, Neves C, Bonner RJ, Bernardo AS, Docherty K, Hoppler S

Publication type: Article

Publication status: Published

Journal: Stem Cell Reports

Year: 2016

Volume: 7

Issue: 4

Pages: 764-776

Print publication date: 11/10/2016

Online publication date: 15/09/2016

Acceptance date: 11/08/2016

Date deposited: 27/10/2016

ISSN (electronic): 2213-6711

Publisher: Cell Press

URL: http://dx.doi.org/10.1016/j.stemcr.2016.08.008

DOI: 10.1016/j.stemcr.2016.08.008

PubMed id: 27641648

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