PT  - JOURNAL ARTICLE
AU  - Yamamoto, Takayoshi
AU  - Kambayashi, Yuta
AU  - Afouda, Boni
AU  - Otsuka, Yuta
AU  - Giuraniuc, Claudiu
AU  - Michiue, Tatsuo
AU  - Hoppler, Stefan
TI  - Positive Feedback Regulation of <em>fzd7</em> Expression Robustly Shapes Wnt Signaling Range in Early Heart Development
AID  - 10.1101/2021.09.12.458649
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.12.458649
4099  - http://biorxiv.org/content/early/2021/09/12/2021.09.12.458649.short
4100  - http://biorxiv.org/content/early/2021/09/12/2021.09.12.458649.full
AB  - Secreted molecules called morphogens govern tissue patterning in a concentration-dependent manner. However, it is still unclear how reproducible patterning can be achieved with diffusing molecules, especially when patterning differentiation of a thin region. Wnt is a morphogen that organizes cardiac development; especially Wnt6 patterns the cardiogenic mesoderm to induce differentiation of a thin pericardium in Xenopus. It is, however, unclear how Wnt6 can pattern such a thin tissue. In this study, we reveal that a Wnt receptor, frizzled7, is expressed in a Wnt-dependent manner in the prospective heart region, and that this receptor-feedback is essential for shaping a steep gradient of Wnt. In addition, the feedback imparts robustness against fluctuations of Wnt ligand production and allows the system to reach a steady state quickly. We also found a Wnt antagonist sFRP1, which is expressed at the opposite side of Wnt source, accumulates on a novel type of heparan sulfate (HS), N-acetyl-rich HS, which is highly presented in the outer of cardiogenic mesoderm, achieving local inhibition of Wnt signaling by restricting sFRP1 spreading. These two intricate regulatory systems restrict Wnt signaling and ensure reproducible patterning of a thin pericardium tissue.Competing Interest StatementThe authors have declared no competing interest.WWnt6SsFRP1WSWnt6-sFRP1HHeparan sulfateSHsFRP1-Heparan sulfateWSHWnt6-sFRP1-Heparan sulfateRFzd7WR2Wnt6-Fzd7