Wnt signalling in Gene Regulatory Networks: How does feedback regulation affect signalling range in embryonic tissues.

Lead Research Organisation: University of Aberdeen
Department Name: Sch of Medicine, Medical Sci & Nutrition

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Publications

10 25 50
 
Description How do WNT signals, extracellular SFRP proteins and FRIZZLED cell-surface receptors regulate each other to guide normal heart development?
Amount £7,000 (GBP)
Funding ID 12969/13787, http://dajf.org.uk/wp-content/uploads/March-2019-Approved-Grants-List.pdf 
Organisation Daiwa Anglo-Japanese Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2019 
End 10/2020
 
Description Dr Pownall presented a research seminar at the National Institute for Basic Biology (Okasaki, 9 May 2018) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Dr Pownall presented her work on Wnt signalling and Heparin sulphates. This encouraged further collaboration leading to the submission of a UKRI JSPS grant application in August 2018.
Year(s) Of Engagement Activity 2018
 
Description Invited Research Seminar at Department of Molecular Biology & Biochemistry and Department of Cardiovascular Surgery Cardiac Regeneration and Therapeutics, University of Ôsaka, Japan 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Presentation of our published and unpublished research results sparked many interesting questions and discussions
Year(s) Of Engagement Activity 2016
 
Description Invited Seminar speaker at Amphibian Research Center, Hiroshima University, Japan 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Presentation of our published and unpublished research results sparked many interesting questions and discussions
Year(s) Of Engagement Activity 2016
 
Description Invited Seminar speaker at Department of Biological Sciences, School of Science, Tokyo University, Japan 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Presentation formed bases of discussions about formal research collaboration. Additionally, presentation of published and unpublished research results sparked many interesting questions and discussions.
Year(s) Of Engagement Activity 2016
 
Description Invited Seminar speaker at Division of Molecular and Development Biology National Institutes of Natural Sciences, Okasaki, Japan 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Presentation of our published and unpublished research results sparked many interesting questions and discussions afterwards.
Year(s) Of Engagement Activity 2016
 
Description Invited research seminar at Department of Biology, University of York 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact University research seminar, discussion of potential future collaborations.
Year(s) Of Engagement Activity 2017
URL https://www.york.ac.uk/biology/news-events/seminars/cellmolecularstructuralbiology/profstefanhoppler...
 
Description Invited speaker at 16th International Xenopus Conference (Crete, August/September 2016) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Important international meeting happening every other year bringing together researchers using Xenopus and other amphibians mainly for fundamental biomedical and biological research. Our invited research seminar sparked many interesting questions and discussions.
Year(s) Of Engagement Activity 2016
URL http://www.xenopus16.com/17789
 
Description Prof. Hoppler presented a double lecture on Wnt signalling to Undergraduate Students at Chuo University Tokyo. (8 May 2018) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact Double Lecture in English on the history, mechanism and biomedical importance of Wnt signalling.
Year(s) Of Engagement Activity 2018
 
Description Research seminar at Okinawa Institute of Science and Technology (25 April 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Research Presentation to Professional Audience
Year(s) Of Engagement Activity 2018
 
Description Research visit and seminar by Dr Takayoshi Yamamoto (Univ. of Tokyo) to Univ. of Aberdeen, Institute of Medical Sciences 6 Dec. 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Dr. Takayoshi Yamamoto, Assistant Professor, Department of Life Sciences, University of Tokyo, Japan presented a talk to about 35 biomedical researchers and post-graduate students in the Institute of Medical sciences.

"The key is the binding partner: the range of Morphogen-mediated signaling is regulated by the antagonists and two different types of heparan sulfate"
Morphogens (e.g. Wnt and BMP) are secreted from source cells and di?use in the extracellular space, making a gradient that organizes embryonic development, regeneration, and diseases. However, how morphogen distribution and signalling range is regulated was poorly understood.
My colleagues have previously shown that Wnt distribution range was expanded by the secreted antagonists (Mii & Taira, 2009). Surprisingly, not only the protein distribution range, but also signal activation range were expanded by the antagonists ("Antagonists" promoted signalling!).
To understand this phenomenon, we focused on an extracellular matrix, heparan sulfate, which have been known to regulate morphogen distribution. We newly identi?ed two types of heparan sulfate (HS) clusters: N-sulfo-rich HS (NS) and N-acetyl-rich HS (NAc), which di?erently modulate Wnt distribution and signalling. NS clusters accumulate Wnt proteins to transduce its signal and make the Wnt distribution shorter mediating endocytosis of Wnt. In contrast, NAc clusters accumulate Frzb (an antagonist of Wnt). Frzb changes Wnt localisation from NS to NAc clusters to prevent Wnt endocytosis, making the Wnt distribution and signaling range broader (Mii and Yamamoto et al., 2017). We have also revealed that this mechanism is applicable to another morphogen, BMP (Yamamoto et al., unpublished). This suggests that the NAc/NS cluster system could be the general molecular basis of morphogen distribution and signalling ranges.
Recent relevant research articles:
• *Mii Y, *Yamamoto T (*co-first author), Takada R, Mizumoto S, Matsuyama M, Yamada S, Takada S, Taira M (2017). Roles of two types of heparan sulfate clusters in Wnt distribution and signaling in Xenopus. Nat Commun. 2017 Dec 7;8(1):1973. doi: 10.1038/s41467-017-02076-0.
• Mii Y, Taira M (2009). Secreted Frizzled-related proteins enhance the diffusion of Wnt ligands and expand their signalling range. Development. 2009 Dec;136(24):4083-8. doi: 10.1242/dev.032524.

Short Bio Sketch Takayoshi Yamamoto:
• Born and brought up in Japan
• Undergraduate degree at Tokyo Institute of Technology, Japan
• Master degree at Laboratory of Cell proliferation in Tokyo Institute of Technology, Japan, with Prof. Takeo Kishimoto on M-phase regulation using Starfish oocyte and egg
• PhD at Laboratory of Animal development at Univ. of Tokyo, Japan, with Prof. Hiroyuki Takeda on the role of cilia in development using Medaka fish
• Post-doc at University of Tokyo, Hongo Campus, Graduate school of Science, Japan, with Assoc. Prof. Masanori Taira on heparan sulfate in Wnt and BMP signalling in Xenopus development
• since 2018, Assistant Professor of Developmental Biology at the University of Tokyo, Komaba Campus, Graduate school of Arts and Sciences, Japan in Prof. Tatsuo Michiue's Department.
Year(s) Of Engagement Activity 2018
 
Description Research visit and seminar by Dr Takayoshi Yamamoto (Univ. of Tokyo) to Univ. of York (10 Dec. 2018) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Dr Yamamoto presented essentially the same talk as he presented in Aberdeen to the researchers at the University of York
Year(s) Of Engagement Activity 2018
 
Description Visit Dr Yusuke Mii (NIBB, Okazaki, Japan) to IMS, University of Aberdeen 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact Visit and talk by Dr Yusuke Mii to the scientists and researchers in the IMS and more widely the University of Aberdeen
Year(s) Of Engagement Activity 2019