Dr Steffen Scholpp
Associate Professor, Cell and Developmental Biology
Living Systems Institute
Living Systems Institute, University of Exeter, Stocker Road, Exeter, EX4 4QD
Tissue development is a key process for life starting from the earliest embryonic stages during which cells differentiate into later organs composing an entire body. An essential component for these developmental processes but also for tissue regeneration and stem cell regulation is the communication of cells by chemical signalling. The highly conserved family of Wnt proteins represents important regulators of cell behaviour, tissue development and homeostasis by inducing responses in a concentration dependent manner. We identified a novel way of spreading of Wnt proteins in vertebrates: Wnt molecules are mobilized on specific cell protrusions so-called cytonemes. These specialized signalling filopodia transmit signal proteins between communicating cells and allow a high degree of control of propagation speed, direction and concentration of the transmitted ligand. The signalling molecules are delivered directly to the receiving cells by a direct-contact model and parameters such as cytoneme length or speed of filopodia formation dictate local Wnt concentration. At the Living Systems Institute, we collaborate with biophysicists using super-resolution microscopy to describe these signalling processes in a quantitative way on a molecular level. As it is very difficult to determine the specific impact of individual parameters in a complex biological system by a purely experimental approach, we interact with mathematicians using computational modelling. Together, we develop a robust mathematical model for the distribution of signal molecules on the basis of signalling filopodia. Due to the conserved nature of vertebrate cell behaviour our results will be relevant to Wnt signalling during human embryonic development and could suggest novel vulnerabilities to Wnt-dependent diseases – a prerequisite for the development of novel therapeutics.
2003 PhD Neurobiology (Hons., summa cum laude), University of Heidelberg, Germany
2017-present Associate Professor of Cell and Developmental Biology, Biosciences, University of Exeter, UK
2009-2016 Emmy-Noether group leader (Assistant Professor) at the Karlsruhe Institute of Technology (KIT), Germany
2004-2009 Postdoctoral Research Fellow with Andrew Lumsden, MRC Centre for Developmental Neurobiology, King’s College London, UK
2003-2004 Postdoctoral Research Associate with M. Brand, Max Planck-Institute of Cell Biology and Genetics (MPI-CBG), Dresden, Germany
1999-2003 PhD in Neurobiology (Laboratory of M. Brand), University of Heidelberg, Germany and Max Planck-Institute of Cell Biology and Genetics (MPI-CBG), Dresden, Germany
Wnt protein (red) on cytoneme tips in vivo
After secretion, developmental signals known as morphogens must travel relatively long distances to form a concentration gradient that the responding tissue uses to acquire positional information. The role of morphogen transport and endocytic trafficking in this process is the subject of intense debate. Wnt proteins regulate developmental processes, tissue regeneration and stem cell maintenance. It has been postulated that Wnt/β-catenin signalling form concentration gradients across responsive tissues and act as morphogens. However, little is known about the transport mechanism for these lipid-modified signalling proteins in vertebrates.
Recently, we showed that Wnt8a is transported on short, actin-based filopodia to contact responding cells and activate signalling during neural plate formation in zebrafish (1). Cdc42/N-Wasp regulates the formation of these Wnt-positive filopodia. Enhanced formation of filopodia increases the effective signalling range of Wnt by facilitating spreading. Consistently, reduction in filopodia leads to a restricted distribution of the ligand and a limited signalling range. Using a numerical simulation, we provide evidence that such a short-range transport system for Wnt has long-range signalling function.
After contact by Wnt/β-catenin positive filopodia, a multi-protein complex at the plasma membrane assembles clustering membrane-bound receptors and intracellular signal transducers into the so-called Lrp6-signalosome. Our imaging studies in live zebrafish embryos showed that the signalosome is a highly dynamic structure, which is continuously assembled and disassembled by a Dvl2-mediated endocytic process (2). We showed that this endocytic process is not only essential for ligand-receptor internalization but also for signaling.
We conclude that a cytoneme-based transport system for Wnt and subsequent endocytosis is important for Wnt/β-catenin signaling and controls anteroposterior patterning of the neural plate during vertebrate gastrulation (3,4).
(1) Stanganello et al., Nature Comms., 2015; (2) Hagemann, et al., J.Cell Sci., 2014; (3) Stanganello and Scholpp, J.Cell Sci., 2016; (4) Brunt and Scholpp, CMLS, 2017
Publications by category
Publications by year
Steffen_Scholpp Details from cache as at 2018-03-17 00:24:54
since 2017 Deputy Director of Postgraduate Research (D-DPGR)
2016 elected member of the KIT convent
2013 - 2014 Coordinator of the research cluster “Neural development and neural stem cells” of the Helmholtz Research Program “BioInterfaces”
2012 - 2013 Spokesman of the Young Investigator Network (YIN); assembly of junior faculties at
2010 - 2016 Member of the PhD Selection Committee for the BioInterfaces Graduate School, KIT
since 2010 Graduate Student Advisor, KIT
2009 - 2011 Organizer of the Internal Seminar Series “On Fish and Technologies”, ITG, KIT
2009 - 2016 Member of the Faculty of Chemistry and Life Science, KIT, Germany
since 2016 Reviewer for BBSRC
since 2014 Scientific reviewer for Research grants of the National Science Centre, NSC Poland
since 2010 Reviewer for Research grants of the German Research Council (DFG)
2010 Scientific reviewer for DFG-Center for Regenerative Therapies, Dresden (CRTD)
since 2016 Scientific editor of Mechanisms of Development (MOD)
since 2015 Scientific editor of Genesis, John Wiley and Sons, Inc
since 2014 Scientific editor of Molecular Science, AIMS Press
since 2011 Associated editor of Frontiers in Neuroscience
Selected activities as referee for scientific journals
Nature Communications; PLoS Biology; PNAS; EMBO reports; J Cell Sci; Development; Stem Cell Reports; Scientific Reports; Developmental Biology; Brain Structure & Function; Neurobiology of Disease; Neural Development; PLoS One; Differentiation; J of Medical Genetics; Cell & Tissue Research; Genesis; Cellular and Molecular Life Science; Development, Genes & Evolution
Number of invited lectures in total
Recently invited lectures
2017 Duke-NUS, Singapore; University of Calgary, Canada; ARUK Oxford,; University of Madrid, Spain, Wnt meeting and PhD summer school, Kobe Japan.
2016 University of Exeter UK, University of Bath, UK, EZPM Lisbon, Portugal, EMBO Wnt meeting, Brno
2015 UCSF, San Francisco, USA; Uni Jena, Germany; Dev. Biol. Soc. Meeting, Nuremberg, Germany; ETH Zürich Switzerland; EMBO workshop, Madrid, Spain; Gordon Research Conference on Developmental Biology, Mount Holyoke College, USA; DanStem Center, Copenhagen; Instituto de Neurociencias, Alicante, Spain.
2011 – 2015 Member of the DFG Research Network 1036: “Mechanism, functions and evolution of Wnt signalling pathways”
2007 Honorary Member of the Royal Microscopical Society (RMS)
2017 Lecturer, Summer School, Jap Soc Dev Biol, Kobe, Japan.
2015 Session Chair, EMBO workshop „Signaling synapsis“, Madrid, Spain.
2014 Session Chair, European Zebrafish PI Meeting, Ein Gedi, Israel.
2013 Organizer, EMBO practical course „Imaging of Neural Development“, KIT, Germany.
Lecturer, Summer School, Jap Soc Dev Biol, Tokyo, Japan.
2012 Lecturer, GfE Summer School, Schloss Reissenburg, Ulm, Germany.
Session Chair, SURF Meeting Biozentrum Basel, Switzerland.
2011 Session Chair, Regional Meeting on Fish Genetics and Development, Landeck, Germany.
2002 Instructor, EMBO Developmental Biology Practical Course, MPI Tübingen, Germany.
Happy Lab Citizen
- BIO2088 Advanced Cell Biology
- Lab projects on molecular and cell biological topics
Former Teaching Responsibilities
|2010-2016||Lecturer and supervisor in BSc and MSc program “Life Science” at the Faculty of Chemistry and Life Science; 1 lecture series per semester, supervision for 2 practical courses per semester at KIT, Germany.|
|2010-2016||Lecturer of Biointerface International Graduate School (BIF-IGS) at KIT, Germany.|
|2013-2016||Lecturer of the International Zebrafish and Medaka course (IZMC) at the EZRC.|
The Scholpp lab in 2017
- Lucy Brunt
- Joana Viales
- Benjamin Mattes
- Lucy Porter
- Simone Schindler
- Bernadett Boesze PhD student (2012-2016)
- Simone Geyer PhD student(2012-2015)
- Anja Hagemann PostDoc (2009-2014)
- Daniela Peukert PhD student(2008-2011)
- Charanya Rengarajan PhD student (2009-2013)
- Eliana Stanganello PhD student, summa cum laude (2011-2015)