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
Giuraniuc CV
(2022)
A mathematical modelling portrait of Wnt signalling in early vertebrate embryogenesis.
in Journal of theoretical biology
Description | Embryonic tissues are patterned by cell-to-cell signalling molecules described as morphogens. We discovered that the morphogen we studied in vertebrate heart development (Wnt6) not only regulates downstream cell fate to induce subsequent differentiation of two (or more) different tissues (in this case heart muscle versus mesothelium), but also regulates its own signalling mechanisms (i.e., regulates positively expression of the cell membrane receptor and regulates negatively expression of a secreted antagonist). Mathematical modelling suggests that these feedback mechanisms function to sharpen the boundary between any two induced cell fates and lead to patterning (i.e., reaching steady state) faster. |
Exploitation Route | Our findings motivate further investigation into the function of Gene Regulatory Networks as part of signalling systems during embryonic patterning. Our use of mathematical modelling may inspire others to apply such approaches to study and understand other medically relevant biological systems. |
Sectors | Education Healthcare Manufacturing including Industrial Biotechology |
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 | 08/2019 |
End | 10/2020 |
Description | 18th International Xenopus Meeting (completely on line) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Invited talk to experts in the research field presenting several of our Xenopus-related research projects relevant for several funding grants. |
Year(s) Of Engagement Activity | 2021 |
URL | https://registrations.hg3conferences.co.uk/hg3/frontend/reg/thome.csp?pageID=70799&eventID=195&trace... |
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 | International Wnt signalling workshop (EMBO) |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Conference of Researchers working on the Wnt signalling pathway, its mechanisms and its function in embryonic development, stem cells and disease. |
Year(s) Of Engagement Activity | 2022 |
URL | https://events.embo.org/20-wnt/ |
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 (University of Tokyo, Komaba Campus, Komaba 3-8-1, Meguro, Tokyo 153-8902, Japan) |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Professional Practitioners |
Results and Impact | Research Seminar |
Year(s) Of Engagement Activity | 2022 |
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 |