第1123回生物科学セミナー

Tissue- and stage-specific Wnt signalling in embryonic development and heart muscle differentiation.

Dr. Stefan Hoppler(Institute of Medical Sciences, University of Aberdeen, Scotland, United Kingdom)

2016年11月28日(月)    16:00-17:00  理学部2号館 201号室   

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 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 challenges the existing paradigm about Wnt target gene regulation.

Recent relevant research articles:
• Mazzotta S., Neves C., Bernardo AS, Docherty K, Hoppler S (in press). Distinctive Roles of Canonical and Noncanonical Wnt Signaling in Human Embryonic Cardiomyocyte Development, Stem Cell Reports (2016), doi:10.1016/j.stemcr.2016.08.008
• 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
• 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