[Seminar] "Context-specific Wnt Signalling in Embryonic Development and Heart Muscle Differentiation” by Prof. Stefan Hoppler

The Wnt pathway is a conserved cell-to-cell signalling mechanism, which is important for embryonic development, stem cell-mediated regeneration and diseases, such as cancer. We study how the same Wnt pathway is used repeatedly in different cellular contexts to instruct different and specific cellular responses.

We have recently established hESC culture to study the role of Wnt signalling in human heart muscle (cardiomyocyte) differentiation. We have confirmed important stage-specific roles for Wnt signalling in regulating human cardiomyocyte differentiation; and additionally we have identified more precise potential roles for individual Wnt signal and Wnt receptor genes.

We use early Xenopus embryos as a model to investigate the molecular mechanisms of tissue- and stage-specific Wnt signalling. We use a high-throughput sequencing approach combining RNA-seq and ChIP-seq to identify tissue-specific direct Wnt target genes. The findings from our whole-genome analysis challenge the existing paradigm about Wnt target gene regulation.

Short Bio Sketch of Stefan Hoppler:

• Born and brought up in Switzerland
• Undergraduate degree in Zoology at Univ. of Zürich, Switzerland
• PhD at MRC Laboratory of Molecular Biology in Cambridge, England, with Mariann Bienz on homeotic genes in Drosophila
• Post-doc at University of Washington in Seattle, USA, with Randy Moon on Wnt signalling in Xenopus development
• Wellcome Trust Research Career Development Fellow, University of Dundee, Scotland
• since 2003 at the University of Aberdeen, Scotland, since 2012 full Professor of Developmental Biology.

Relevant research articles from Hoppler group:

• Nakamura Y., Alves E., Veenstra GJ, Hoppler S (2016). Tissue- and stage-specific cellular context regulates Wnt target gene expression subsequent to β‑catenin recruitment to cis-regulatory modules. Development 143, 1914-1925. doi:10.1242/dev.131664
• Mazzotta S., Neves C., Bernardo AS, Docherty K, Hoppler S (2016). Distinctive Roles of Canonical and Noncanonical Wnt Signaling in Human Embryonic Cardiomyocyte Development, Stem Cell Reports (2016), 7, 1-13. doi:10.1016/j.stemcr.2016.08.008
• Gibb N., Lavery D.L. and Hoppler, S. (2013). Sfrp1 promotes cardiomyocyte differentiation in Xenopus, via negative feedback regulation of Wnt signalling. Development, 140, 1537-1549. doi:10.1242/dev.088047