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BEGIN:VEVENT
DTSTAMP:20260506T081036Z
DTSTART;VALUE=DATE-TIME:20240515T130000
DTEND;VALUE=DATE-TIME:20240515T140000
SUMMARY:BMS Seminar: Challenging Spemann’s idea: Cytoneme-mediated transp
 ort of active Wnt5b/Ror2 complexes\, Professor Steffen Scholpp FRSB\, Li
 ving System Institute\, School of Biosciences\, University of Exeter
TZID:Europe/London
UID:20240515-8a17841b8defef98018df57fc01f1164@warwick.ac.uk
CREATED:20240410T102358Z
DESCRIPTION:Abstract: Chemical signalling is the primary means by which c
 ells communicate in the embryo. Precisely 100 years ago\, Hans Spemann p
 ostulated the underlying principle\, which refers to a group of ligand-p
 roducing cells and a group of cells that respond to this signal because 
 they express the appropriate receptors. Consequently\, cells and tissues
  lacking the receptors are considered non-responsive or blind. The conce
 pt still dominates our current thinking that signal activation occurs in
  responsive cells but not in non-responsive cells\, allowing for precise
  tissue specification\, organ development\, and formation of the entire 
 embryonic body. In the zebrafish embryo\, Wnt5b binds to the receptor Ro
 r2 to trigger the Wnt/Planar Cell Polarity (Wnt/PCP) signalling pathway 
 to regulate tissue polarity and cell migration. However\, it is still un
 clear how this lipophilic ligand is transported from the source cells th
 rough the aqueous extracellular space to the target tissue. Here\, we sh
 ow that Wnt5b is loaded on long signalling filopodia\, also known as cyt
 onemes. Surprisingly\, we also find that the vital co-receptor Ror2 is l
 ocalised to the same cytonemes. The active Wnt5b/Ror2 complexes are form
 ed in the producing cell and handed over from these cytonemes to the rec
 eiving cell. Then\, the receiving cell activates Wnt/PCP signalling\, re
 gardless of whether the cell expresses functional receptors. On the tiss
 ue level\, we further show that cytoneme-dependent spreading of active W
 nt5b/Ror2 affects convergence and extension in the zebrafish gastrula. I
 n parallel\, we find that precisely the same mechanism operates in human
  gastric cancer tumours\, allowing cancer-associated fibroblasts to infl
 uence the behaviour of gastric cancer cells. We suggest that cytoneme-me
 diated transfer of ligand-receptor complexes is a vital mechanism for pa
 racrine signalling and thus challenges the long-standing concept of char
 acterising responsive and non-responsive tissues based solely on the exp
 ression of the receptors. Biography: Steffen Scholpp is a Professor of C
 ell and Developmental Biology at the Living Systems Institute\, Universi
 ty of Exeter\, studying intercellular communication in zebrafish embryos
  and human organoids. He focuses on cell-biological mechanisms regulatin
 g the distribution and function of signalling molecules in developing ti
 ssues. By using fluorescently tagged Wnt ligands\, he was able to descri
 be for the first time the dynamic spreading of Wnt signalling on filopod
 ia between cells in real time. Based on these findings\, he investigates
  the underlying molecular mechanism of the emergence of these Wnt8a cyto
 nemes in zebrafish. He further explores the function of Wnt cytonemes in
  gastric cancer and shows that cytonemes transport Wnt3 between cancer c
 ells. Recently\, his team showed that cytoneme can disseminate fully ass
 embled and active Wnt5/Ror2 complexes to regulate Wnt/PCP signalling in 
 the target cells in zebrafish and gastric cancer. Cytoneme-based transpo
 rt of signalling proteins is now considered so fundamental that SS's wor
 k now appears in a dedicated chapter in Scott Gilbert's textbook 'Develo
 pmental Biology'. His team has considerable experience in in vivo super-
 resolution imaging. He collaborates with the microscopy company Leica MS
  to adapt new quantitative imaging technologies and AstraZeneca to estab
 lish precise genome editing in zebrafish. In conclusion\, he has over 20
  years of experience analysing morphogen signalling with over 50 publica
 tions\, h-index 33\, and over 4\,200 citations.
LOCATION:IBRB Lecture Theatre
CATEGORIES:BiomedicalSciences,DivisionalSeminars
LAST-MODIFIED:20240410T102358Z
ORGANIZER;CN=Jas Bains:
END:VEVENT
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