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Professor Steffen Scholpp

Professor of Cell and Developmental Biology

7451

+44 (0)1392 727451

Living Systems Institute T02.12

Living Systems Institute, University of Exeter, Stocker Road, Exeter, EX4 4QD

Overview

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 Wnt proteins in vertebrates: Wnt molecules are mobilized on specific cell protrusions known as 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.

In our research, we use the zebrafish embryo to investigate how intercellular Wnt protein transport is regulated and how signals are subsequently delivered to the target cell in a living vertebrate organism. By understanding Wnt dissemination mechanisms, we will be able to control Wnt signalling in development, and regeneration. This research is funded by the Biotechnology and Biological Sciences Research Council (BBSRC).

We further use gastric cancer cells to investigate how cytonemes mobilize Wnts in tumour tissue. Our research will open up new strategies to control Wnt signalling by altering its transport route in the tumour microenvironment. Our research is supported by the Medical Research Council (MRC).

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.

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Qualifications

2009-2016 Emmy-Noether Research Group Leader (Assistant Professor)

2003 PhD Neurobiology (Hons., summa cum laude), University of Heidelberg, Germany

Career

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 Prof Andrew Lumsden, FRS, MRC Centre for Developmental Neurobiology, King’s College London, UK

2003-2004 Postdoctoral Research Associate with Prof Michael Brand, Max Planck-Institute of Cell Biology and Genetics (MPI-CBG), Dresden, Germany

2003 PhD Neurobiology (Hons., summa cum laude), University of Heidelberg, Germany

1999-2003 PhD student in Neurobiology (Laboratory of Prof Michael Brand), University of Heidelberg, Germany and Max Planck-Institute of Cell Biology and Genetics (MPI-CBG), Dresden, Germany

Links

Wnt protein (red) on cytoneme tips in vivo

Research

Research interests

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 forms 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 known as cytonemes to contact responding cells and activate signalling during neural plate formation in zebrafish (1).Wnt/ Ror2 signalling regulates the formation of these Wnt cytonemes (5). Enhanced formation of cytonemes increases the effective signalling range of Wnt by facilitating spreading. Consistently, reduction in cytonemes 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 a long-range signalling function.

We also showed that Wnt cytonemes are essential to disseminate Wnt signalling in gastric tumours. In this tissue, fibroblasts produce Wnts and distribute them via a dynamic cytoneme network within the cancer tissue to regulate proliferation and metastasis.

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 signalling.

We conclude that a cytoneme-based transport system for Wnt and subsequent endocytosis is important for Wnt/β-catenin signalling in development and disease (3,4,6).

(1) Stanganello et al., Nature Comms., 2015; (2) Hagemann, et al., J.Cell Sci., 2014; (3) Zhang and Scholpp, 2019; (4) Brunt and Scholpp, CMLS, 2017; (5) Mattes et al., eLife, 2018. (6) Brunt et al., Nat Comms 2021

Research projects

OPEN POSITIONS:

We're recruiting talented graduates from all areas of bioscience to become MSc students, PhD students and postdoctoral researchers in our lab. Contact us to talk about possibilities.

Join our team!

Research grants

2022 BBSRC
Establishing precise genome editing in zebrafish and its application to advance understanding of the Wnt/PCP signalling pathway
2022 BBSRC
BBSRC Responsive Mode, BB/W015420/1
2021 MRC
MRC Confidence in Concept (CiC) Project with AstraZeneca
2020 BBSRC
Lattice-based Microscopy to analyse subcellular dynamics in living specimen;: BBSRC 19-ALERT Mid-range equipment initiative; 2020-2021; BB/T017899/1
2019 Medical Research Council
Deciphering the molecular mechanism of Wnt trafficking in gastric cancer; MRC Research Grant; 2019-2022; MR/S007970/1
2019 BBSRC
Quantitative analysis of cytoneme-based Wnt trafficking and signalling in vivo; BBSRC Responsive Mode; 2019-2022; BB/S016295/1
2019 BBSRC
HPF to enable a high-quality ultrastructural analysis of biological samples; BBSRC 18-ALERT Mid-range equipment initative; 2019-2020; BB/R019499/1
2018 BBSRC
A Single Molecule Detection Unit to perform in vivo FCS and FLIM-FRET analysis in zebrafish; BBSRC 17-ALERT Mid-range equipment initiative; 2018-2019; BB/R013764/1
2017 Wellcome Trust
CBMA Seed Corn Award, 2018; WT105618MA

Publications

Key publications | Publications by category | Publications by year

Key publications

Liu T-L, Upadhyayula S, Milkie D, Singh V, Wang K, Swineburn I, Scholpp S, Megason S, Kirchhausen T, Betzig E, et al (In Press). Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms. Science

Rogers S, Zhang C, Anagnostidis V, Liddle C, Fishel ML, Gielen F, Scholpp S (2023). Cancer-associated fibroblasts influence Wnt/PCP signaling in gastric cancer cells by cytoneme-based dissemination of ROR2. Proceedings of the National Academy of Sciences, 120(39). Abstract.

Winter MJ, Ono Y, Ball JS, Walentinsson A, Michaelsson E, Tochwin A, Scholpp S, Tyler CR, Rees S, Hetheridge MJ, et al (2022). A Combined Human in Silico and CRISPR/Cas9-Mediated in Vivo Zebrafish Based Approach to Provide Phenotypic Data for Supporting Early Target Validation. Frontiers in Pharmacology, 13

Routledge D, Rogers S, Ono Y, Brunt L, Meniel V, Tornillo G, Ashktorab H, Phesse TJ, Scholpp S (2022). The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer. eLife, 11 Abstract.

Brunt L, Greicius G, Rogers S, Evans BD, Virshup DM, Wedgwood KCA, Scholpp S (2021). Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling. Nat Commun, 12(1). Abstract. Author URL.

Bosze B, Ono Y, Mattes B, Sinner C, Gourain V, Thumberger T, Tlili S, Wittbrodt J, Saunders TE, Strähle U, et al (2020). Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish. Histochemistry and Cell Biology, 154(5), 463-480. Abstract.

Publications by category

Journal articles

Gardilla AC, Sanchez D, Brunt L, Scholpp S (In Press). From top to bottom: Cell polarity in Hedgehog and Wnt trafficking. BMC Biology

Rogers S, Scholpp S (2022). Vertebrate Wnt5a – at the crossroads of cellular signalling. Seminars in Cell & Developmental Biology, 125, 3-10.

Sutton G, Kelsh RN, Scholpp S (2021). Review: the Role of Wnt/β-Catenin Signalling in Neural Crest Development in Zebrafish. Frontiers in Cell and Developmental Biology, 9 Abstract.

Cavallo JC, Scholpp S, Flegg MB (2020). Delay-driven oscillations via Axin2 feedback in the Wnt/β-catenin signalling pathway. J Theor Biol, 507

The Wnt signalling pathway plays an important role in development, disease, and normal tissue function. Mathematical models for Wnt signalling have predominantly focused on quantitatively predicting changes in steady-state β-catenin concentrations (the main downstream protein regulated by canonical Wnt signalling). One of the genes targeted for expression by Wnt/β-catenin signalling is the negative Wnt regulator Axin2. Recently, a number of authors have indicated a potential theoretical role of Axin2 feedback to induce oscillatory behaviour in the pathway and this has been observed in a number of detailed mathematical models. Due to the complexity of these models, the investigations to date have been limited to numerical experiments and parameter sensitivity analyses. In this manuscript, we study the fundamental structure of the dynamical system underlying the Wnt signalling mechanism with Axin2 feedback to gain some insight into why and when oscillations occur in models with this structure. We semi-rigorously analyse three simple models and, for these models, gain deep understanding of the characteristic set of conditions that are necessary and sufficient for oscillations to be induced. We discuss the possible biological consequences of these findings for Wnt signalling pathway oscillations. They include; to promote oscillations (1) Keeping all other parameters constant, the Wnt signal strength should neither be too high or too low but within a single finite window of values, (2) Wnt receptor complexes should fully deactivate Axin rather than temporarily deconstruct it from other scaffold proteins, (3) in the absence of stochastic effects or more complicated mechanisms, a critical delay in Axin2 feedback in the system is necessary, (4) Deactivation of Axin by the Wnt receptor complex needs to be critically efficient relative to β-catenin removal by Axin, and (5) conditions necessary are less strict if Axin2 feedback occurs after a fixed time rather than a Poisson-distributed time with the same average.

Abstract. Author URL.

Alshami IJJ, Ono Y, Correia A, Hacker C, Lange A, Scholpp S, Kawasaki M, Ingham PW, Kudoh T (2020). Development of the electric organ in embryos and larvae of the knifefish, Brachyhypopomus gauderio. Developmental Biology, 466(1-2), 99-108.

Scholpp S (2020). Introduction: in vivo cell biology in zebrafish. Histochem Cell Biol, 154(5), 457-461. Author URL.

Rosenbauer J, Zhang C, Mattes B, Reinartz I, Wedgwood K, Schindler S, Sinner C, Scholpp S, Schug A (2020). Modeling of Wnt-mediated tissue patterning in vertebrate embryogenesis. PLOS Computational Biology, 16(6), e1007417-e1007417.

Dawes ML, Soeller C, Scholpp S (2020). Studying molecular interactions in the intact organism: fluorescence correlation spectroscopy in the living zebrafish embryo. HISTOCHEMISTRY AND CELL BIOLOGY, 154(5), 507-519. Author URL.

Brunt L, Greicius G, Evans BD, Virshup DM, Wedgwood KCA, Scholpp S (2020). Vangl2 regulates the dynamics of Wnt cytonemes in vertebrates. Abstract.

Zhang C, Scholpp S (2019). Cytonemes in development. Current Opinion in Genetics and Development, 57, 25-30. Abstract.

Routledge D, Scholpp S (2019). Mechanisms of intercellular Wnt transport. Development, 146(10). Abstract. Author URL.

Mattes B, Scholpp S (2018). Emerging role of contact-mediated cell communication in tissue development and diseases. Histochemistry and Cell Biology, 150, 431-442. Abstract.

Brunt L, Scholpp S (2018). The function of endocytosis in Wnt signaling. Cellular and Molecular Life Sciences, 75(5), 785-795. Abstract.

Scholpp S (2018). Wnt/PCP controls spreading of Wnt/β-catenin signals by cytonemes in vertebrates. eLife

Stanganello E, Scholpp S (2016). Role of cytonemes in Wnt transport. J Cell Sci, 129(4), 665-672. Abstract. Author URL.

Brinkmann E-M, Mattes B, Kumar R, Hagemann AIH, Gradl D, Scholpp S, Steinbeisser H, Kaufmann LT, Özbek S (2016). Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation. J Biol Chem, 291(26), 13730-13742. Abstract. Author URL.

Stanganello E, Hagemann AIH, Mattes B, Sinner C, Meyen D, Weber S, Schug A, Raz E, Scholpp S (2015). Filopodia-based Wnt transport during vertebrate tissue patterning. Nat Commun, 6 Abstract. Author URL.

Hirschbiel AF, Geyer S, Yameen B, Welle A, Nikolov P, Giselbrecht S, Scholpp S, Delaittre G, Barner-Kowollik C (2015). Photolithographic patterning of 3D-formed polycarbonate films for targeted cell guiding. Adv Mater, 27(16), 2621-2626. Abstract. Author URL.

Rengarajan C, Matzke A, Reiner L, Orian-Rousseau V, Scholpp S (2014). Endocytosis of Fgf8 is a double-stage process and regulates spreading and signaling. PLoS One, 9(1). Abstract. Author URL.

Hagemann AIH, Kurz J, Kauffeld S, Chen Q, Reeves PM, Weber S, Schindler S, Davidson G, Kirchhausen T, Scholpp S, et al (2014). In vivo analysis of formation and endocytosis of the Wnt/β-Catenin signaling complex in zebrafish embryos. Development, 141(19), e1907-e1907.

Hagemann AIH, Kurz J, Kauffeld S, Chen Q, Reeves PM, Weber S, Schindler S, Davidson G, Kirchhausen T, Scholpp S, et al (2014). In vivo analysis of formation and endocytosis of the Wnt/β-catenin signaling complex in zebrafish embryos. J Cell Sci, 127(Pt 18), 3970-3982. Abstract. Author URL.

Chatterjee M, Guo Q, Weber S, Scholpp S, Li JY (2014). Pax6 regulates the formation of the habenular nuclei by controlling the temporospatial expression of Shh in the diencephalon in vertebrates. BMC Biol, 12

BACKGROUND: the habenula and the thalamus are two critical nodes in the forebrain circuitry and they connect the midbrain and the cerebral cortex in vertebrates. The habenula is derived from the epithalamus and rests dorsally to the thalamus. Both epithalamus and thalamus arise from a single diencephalon segment called prosomere (p)2. Shh is expressed in the ventral midline of the neural tube and in the mid-diencephalic organizer (MDO) at the zona limitans intrathalamica between thalamus and prethalamus. Acting as a morphogen, Shh plays an important role in regulating cell proliferation and survival in the diencephalon and thalamic patterning. The molecular regulation of the MDO Shh expression and the potential role of Shh in development of the habenula remain largely unclear. RESULTS: We show that deleting paired-box and homeobox-containing gene Pax6 results in precocious and expanded expression of Shh in the prospective MDO in fish and mice, whereas gain-of-function of pax6 inhibits MDO shh expression in fish. Using gene expression and genetic fate mapping, we have characterized the expression of molecular markers that demarcate the progenitors and precursors of habenular neurons. We show that the thalamic domain is shifted dorsally and the epithalamus is missing in the alar plate of p2 in the Pax6 mutant mouse. Conversely, the epithalamus is expanded ventrally at the expense of the thalamus in mouse embryos with reduced Shh activity. Significantly, attenuating Shh signaling largely rescues the patterning of p2 and restores the epithalamus in Pax6 mouse mutants, suggesting that Shh acts downstream of Pax6 in controlling the formation of the habenula. Similar to that found in the mouse, we show that pax6 controls the formation of the epithalamus mostly via the regulation of MDO shh expression in zebrafish. CONCLUSIONS: Our findings demonstrate that Pax6 has an evolutionarily conserved function in establishing the temporospatial expression of Shh in the MDO in vertebrates. Furthermore, Shh mediates Pax6 function in regulating the partition of the p2 domain into the epithalamus and thalamus.

Abstract. Author URL.

Chen Q, Su Y, Wesslowski J, Hagemann AI, Ramialison M, Wittbrodt J, Scholpp S, Davidson G (2014). Tyrosine phosphorylation of LRP6 by Src and Fer inhibits Wnt/β-catenin signalling. EMBO Rep, 15(12), 1254-1267. Abstract. Author URL.

Efremov AN, Stanganello E, Welle A, Scholpp S, Levkin PA (2013). Micropatterned superhydrophobic structures for the simultaneous culture of multiple cell types and the study of cell-cell communication. Biomaterials, 34(7), 1757-1763. Abstract. Author URL.

Schmidt R, Strähle U, Scholpp S (2013). Neurogenesis in zebrafish - from embryo to adult. Neural Dev, 8 Abstract. Author URL.

Hagemann AIH, Scholpp S (2012). The Tale of the Three Brothers - Shh, Wnt, and Fgf during Development of the Thalamus. Front Neurosci, 6 Abstract. Author URL.

Mattes B, Weber S, Peres J, Chen Q, Davidson G, Houart C, Scholpp S (2012). Wnt3 and Wnt3a are required for induction of the mid-diencephalic organizer in the caudal forebrain. Neural Dev, 7 Abstract. Author URL.

Peukert D, Weber S, Lumsden A, Scholpp S (2011). Lhx2 and Lhx9 determine neuronal differentiation and compartition in the caudal forebrain by regulating Wnt signaling. PLoS Biol, 9(12). Abstract. Author URL.

Scholpp S, Lumsden A (2010). Building a bridal chamber: development of the thalamus. Trends Neurosci, 33(8), 373-380. Abstract. Author URL.

Peukert D, Scholpp S (2010). Ontogenesis of the brain: the development of the thalamus - the gateway to consciousness. BioSpektrum, 16(6), 639-643. Abstract.

Fassier C, Hutt JA, Scholpp S, Lumsden A, Giros B, Nothias F, Schneider-Maunoury S, Houart C, Hazan J (2010). Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway. Nat Neurosci, 13(11), 1380-1387. Abstract. Author URL.

Yu SR, Burkhardt M, Nowak M, Ries J, Petrásek Z, Scholpp S, Schwille P, Brand M (2009). Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules. Nature, 461(7263), 533-536. Abstract. Author URL.

Scholpp S, Delogu A, Gilthorpe J, Peukert D, Schindler S, Lumsden A (2009). Her6 regulates the neurogenetic gradient and neuronal identity in the thalamus. Proc Natl Acad Sci U S A, 106(47), 19895-19900. Abstract. Author URL.

Scholpp S (2008). Hedgehogs, Fluorescence Imaging & Brain Development. infocus Magazine, 66-75.

Wendl T, Adzic D, Schoenebeck JJ, Scholpp S, Brand M, Yelon D, Rohr KB (2007). Early developmental specification of the thyroid gland depends on han-expressing surrounding tissue and on FGF signals. Development, 134(15), 2871-2879. Abstract. Author URL.

Scholpp S, Foucher I, Staudt N, Peukert D, Lumsden A, Houart C (2007). Otx1l, Otx2 and Irx1b establish and position the ZLI in the diencephalon. Development, 134(17), 3167-3176. Abstract. Author URL.

Erickson T, Scholpp S, Brand M, Moens CB, Waskiewicz AJ (2007). Pbx proteins cooperate with Engrailed to pattern the midbrain-hindbrain and diencephalic-mesencephalic boundaries. Dev Biol, 301(2), 504-517. Abstract. Author URL.

Scholpp S, Wolf O, Brand M, Lumsden A (2006). Hedgehog signalling from the zona limitans intrathalamica orchestrates patterning of the zebrafish diencephalon. Development, 133(5), 855-864. Abstract. Author URL.

Scholpp S, Brand M (2004). Endocytosis controls spreading and effective signaling range of Fgf8 protein. Curr Biol, 14(20), 1834-1841. Abstract. Author URL.

Scholpp S, Groth C, Lohs C, Lardelli M, Brand M (2004). Zebrafish fgfr1 is a member of the fgf8 synexpression group and is required for fgf8 signalling at the midbrain-hindbrain boundary. Dev Genes Evol, 214(6), 285-295. Abstract. Author URL.

Scholpp S, Lohs C, Brand M (2003). Engrailed and Fgf8 act synergistically to maintain the boundary between diencephalon and mesencephalon (vol 130, pg 4881, 2003). DEVELOPMENT, 130(21), 5293-5293. Author URL.

Scholpp S, Lohs C, Brand M (2003). Engrailed and Fgf8 act synergistically to maintain the boundary between diencephalon and mesencephalon. Development, 130(20), 4881-4893.

Specification of the forebrain, midbrain and hindbrain primordia occurs during gastrulation in response to signals that pattern the gastrula embryo. Following establishment of the primordia, each brain part is thought to develop largely independently from the others under the influence of local organizing centers like the midbrain-hindbrain boundary (MHB, or isthmic) organizer. Mechanisms that maintain the integrity of brain subdivisions at later stages are not yet known. To examine such mechanisms in the anterior neural tube, we have studied the establishment and maintenance of the diencephalic-mesencephalic boundary (DMB). We show that maintenance of the DMB requires both the presence of a specified midbrain and a functional MHB organizer. Expression of pax6.1, a key regulator of forebrain development, is posteriorly suppressed by the Engrailed proteins, Eng2 and Eng3. Mis-expression of eng3 in the forebrain primordium causes downregulation of pax6.1, and forebrain cells correspondingly change their fate and acquire midbrain identity. Conversely, in embryos lacking both eng2 and eng3, the DMB shifts caudally into the midbrain territory. However, a patch of midbrain tissue remains between the forebrain and the hindbrain primordia in such embryos. This suggests that an additional factor maintains midbrain cell fate. We find that Fgf8 is a candidate for this signal, as it is both necessary and sufficient to repress pax6.1 and hence to shift the DMB anteriorly independently of the expression status of eng2/eng3. By examining small cell clones that are unable to receive an Fgf signal, we show that cells in the presumptive midbrain neural plate require an Fgf signal to keep them from following a forebrain fate. Combined loss of both Eng2/Eng3 and Fgf8 leads to complete loss of midbrain identity, resulting in fusion of the forebrain and the hindbrain primordia. Thus, Eng2/Eng3 and Fgf8 are necessary to maintain midbrain identity in the neural plate and thereby position the DMB. This provides an example of a mechanism needed to maintain the subdivision of the anterior neural plate into forebrain and midbrain.

Abstract. Author URL.

Scholpp S, Brand M (2003). Integrity of the midbrain region is required to maintain the diencephalic-mesencephalic boundary in zebrafish no isthmus/pax2.1 mutants. Dev Dyn, 228(3), 313-322. Abstract. Author URL.

Picker A, Scholpp S, Böhli H, Takeda H, Brand M (2002). A novel positive transcriptional feedback loop in midbrain-hindbrain boundary development is revealed through analysis of the zebrafish pax2.1 promoter in transgenic lines. Development, 129(13), 3227-3239.

The pax2.1 gene encodes a paired-box transcription factor that is one of the earliest genes to be specifically activated in development of the midbrain and midbrain-hindbrain boundary (MHB), and is required for the development and organizer activity of this territory. To understand how this spatially restricted transcriptional activity of pax2.1 is achieved, we have isolated and characterized the pax2.1-promoter using a lacZ and a GFP reporter gene in transient injection assays and transgenic lines. Stable transgenic expression of this reporter gene shows that a 5.3-kb fragment of the 5' region contains most, but not all, elements required for driving pax2.1 expression. The expressing tissues include the MHB, hindbrain, spinal cord, ear and pronephros. Transgene activation in the pronephros and developing ear suggests that these pax2.1-expressing tissues are composed of independently regulated subdomains. In addition, ectopic but spatially restricted activation of the reporter genes in rhombomeres 3 and 5 and in the forebrain, which do not normally express endogenous pax2.1, demonstrates the importance of negative regulation of pax2.1. Comparison of transgene expression in wild-type and homozygous pax2.1 mutant no isthmus (noi) embryos reveals that the transgene contains control element(s) for a novel, positive transcriptional feedback loop in MHB development. Transcription of endogenous pax2.1 at the MHB is known to be initially Pax2.1 independent, during activation in late gastrulation. In contrast, transgene expression requires the endogenous Pax2.1 function. Transplantations, mRNA injections and morpholino knock-down experiments show that this feedback regulation of pax2.1 transcription occurs cell-autonomously, and that it requires eng2 and eng3 as known targets for Pax2.1 regulation. We suggest that this novel feedback loop may allow continuation of pax2.1 expression, and hence development of the MHB organizer, to become independent of the patterning machinery of the gastrula embryo.

Abstract. Author URL.

Scholpp S, Brand M (2001). Morpholino-induced knockdown of zebrafish engrailed genes eng2 and eng3 reveals redundant and unique functions in midbrain--hindbrain boundary development. Genesis, 30(3), 129-133. Author URL.

Chapters

Rogers S, Scholpp S (2021). Preserving Cytonemes for Immunocytochemistry of Cultured Adherent Cells. In (Ed) , 183-190. Abstract. Author URL.

Scholpp S, Shimogori T (2013). Building the gateway to consciousness-about the development of the thalamus. In (Ed) . Author URL.

Scholpp S, Brand M (2009). Neural Patterning: Midbrain-Hindbrain Boundary. In (Ed) Encyclopedia of Neuroscience, 205-211. Abstract.

Conferences

Scholpp S, Brunt L (2022). PCP/VANGL2 SIGNALLING REGULATES WNT CYTONEMES. Author URL.

Mattes B, Scholpp S (2017). Towards deciphering the molecular mechanism regulating Wnt ligand trafficking. Author URL.

Reinartz I, Sinner C, Stanganello E, Mattes B, Scholpp S, Schug A (2016). 3D Simulations of Morphogen Transport in an Early Fish Embryo. Author URL.

Heeren-Hagemann A, Kurz J, Kauffeld S, Chen Q, Reeves P, Weber S, Schindler S, Davidson G, Kirchhausen T, Scholpp S, et al (2016). In vivo analysis of formation and endocytosis of the Wnt/β-Catenin signaling complex in zebrafish embryos. Author URL.

Sinner C, Reinartz I, Boesze B, Scholpp S, Schug A (2016). Dynamic Simulations of Cell Migration with Applications to Brain Development. Author URL.

Sinner C, Stanganello E, Hagemann AIH, Mattes B, Meyen D, Weber S, Raz E, Scholpp S, Schug A (2015). Monte Carlo Simulation of Wnt Propagation by a Novel Transport Mechanism Complementing a Joint Experimental Study. Author URL.

Hagemann A, Kurz J, Kauffeld S, Chen Q, Reeves P, Davidson G, Kirchhausen T, Scholpp S (2014). In-vivo analysis of formation and endocytosis of the Wnt/β-catenin signaling complex in zebrafish embryos. Author URL.

Hagemann AI, Schindler S, Scholpp S (2010). The clathrin adaptor-protein subunit ap2m1 regulates canonical Wnt signalling in early neural development of the zebrafish. Author URL.

Heinze KG, Schlopp S, Brand M, Schwille P (2004). Probing intercellular pathways and propagation of Fgf8 signalling protein during embryogenesis by FCS. Author URL.

Scholpp S, Brand M (2003). Endocytosis controls propagation of Fgf8 during zebrafish embryogenesis. Author URL.

Reports

Scholpp S, Poggi L, Zigman M (2013). Brain on the stage - spotlight on nervous system development in zebrafish: EMBO practical course, KIT, Sept. 2013. Abstract. Author URL.

Blackshaw S, Scholpp S, Placzek M, Ingraham H, Simerly R, Shimogori T (2010). Molecular pathways controlling development of thalamus and hypothalamus: from neural specification to circuit formation. 5 pages. Abstract. Author URL.

Publications by year

In Press

Gardilla AC, Sanchez D, Brunt L, Scholpp S (In Press). From top to bottom: Cell polarity in Hedgehog and Wnt trafficking. BMC Biology

2023

Piers TM, Namboori SC, Bhinge A, Killick R, Scholpp S (2023). Wnt-7a-positive dendritic cytonemes induce synaptogenesis in cortical neurons. Abstract.

2022

Rogers S, Zhang C, Anagnostidis V, Fishel M, Gielen F, Scholpp S (2022). Cancer-associated fibroblast-derived ROR2 induces WNT/PCP activation and polarized migration in receiving gastric cancer cells.

Zhang C (2022). Cytoneme-mediated transport of active Wnt5b/Ror2 complexes in zebrafish.

Chemical signalling is the primary means by which cells communicate in embryonic development. The underlying principle refers to a ligand-producing group of cells and a competent receiver group, which can respond to this signal because they express the specific receptor. The Wnt/Planar Cell Polarity (Wnt/PCP) signalling pathway controls tissue polarity and cell movement by activating several downstream cascades, including c-Jun N-terminal kinase (JNK) signalling. In the zebrafish embryo, the Wnt/PCP ligand Wnt5b binds to its bona fide receptor Ror2 to trigger the Wnt/PCP signalling cascade. However, it is still unclear how this lipophilic ligand is transported from a localised source through the aqueous extracellular space. This is essential because paracrine Wnt/PCP signalling restructures the embryonic tissue leading to convergence along one axis and extension along the perpendicular axis.
In this thesis, I show that Wnt5b, together with its cognate receptor Ror2, is loaded on signalling filopodia, better known as cytonemes. Wnt5b/Ror2 complex on producing cells can control the emergence of cytoneme and maintain the longer cytonemes. These cytonemes extend several tens of micrometres in the zebrafish gastrula. The Wnt5b/Ror2 complex is handed over from the cytoneme to the receiving cell. The transferred Wnt5b/Ror2 complex remains intact during transport and can trigger Wnt/PCP signalling in the receiving cells, regardless of whether the cell expresses functional receptors. On the tissue level, I further show that cytoneme-dependent spreading of active Wnt5b/Ror2 affects convergence and extension in the zebrafish gastrula. Therefore, I suggest that cytoneme-mediated transfer of ligand-receptor complexes is a vital mechanism for paracrine signalling in a tissue, even if the receiving cells are considered non-responsive by lacking a functional receptor. Thus my work challenges the long-standing concept of characterising responsive and non-responsive tissues based solely on the expression of the receptors.

Abstract.

Zhang C, Brunt L, Rogers S, Scholpp S (2022). Cytoneme-mediated transport of active Wnt5b/Ror2 complexes in zebrafish gastrulation.

Routledge D (2022). Extracellular trafficking of Wnt signals in gastric cancer.

Wnt proteins are secreted glycoproteins which signal in a tissue to regulate multiple cellular processes, such as cell differentiation, migration, and proliferation. However, post-translational modifications result in Wnt ligands being hydrophobic in nature.
Thus, their ability to freely diffuse in the aqueous extracellular environment is restricted, and alternative mechanisms of transport have been proposed. In this thesis, I investigate and characterise the use of signalling filopodia – termed cytonemes – in the intercellular transport of Wnt3 ligands by gastric cancer cells, which display overactivated Wnt/β-catenin signalling. Additionally, I identify the membrane scaffolding protein Flotillin-2 (Flot2), which is overexpressed in gastric cancers, as a novel positive regulator of Wnt cytoneme formation and consequently proliferation. Mechanistically, I show that Flot2 is required for the intracellular transport, membrane localisation and thus signalling of the Wnt co-receptor Ror2; a known regulator of Wnt cytonemes.
In parallel, I show that Flot2 also has a function in transducing signals in the Wnt- receiving cell. Here, Flot2 co-localises with the Wnt co-receptor Lrp6 and is involved in its endocytic uptake. Additionally, Flot2 knockdown results in the perinuclear accumulation of Lrp6 and its absence from recycling endosomes. Therefore, I suggest Flot2 may also be involved in the endosomal transport of Lrp6 following internalisation.
Finally, following my observed co-localisations of both Ror2 and Lrp6 with Flot2, I found that these Wnt co-receptors co-localise with one another, as well as the cognate Wnt receptor Frizzled 7, in Flot2 microdomains. Expression of a mutant Ror2 missing its cysteine-rich domain, however, causes loss of co-localisation with Lrp6 and perturbed Wnt/β-catenin signalling. Together, these findings led me to propose a model whereby Frizzled 7, Ror2 and Lrp6 all interact and form one large complex, which I have termed the Wnt Receptor Supercomplex (WRS). I hypothesise that these receptors may interact, even in the absence of Wnt ligands, to regulate one another’s binding affinities for either Wnt/β-catenin or Wnt/PCP ligands. Here, I propose that flotillin microdomains provide the scaffold necessary for these interactions.

Abstract.

Scholpp S, Brunt L (2022). PCP/VANGL2 SIGNALLING REGULATES WNT CYTONEMES. Author URL.

Routledge D, Rogers S, Ashktorab H, Phesse TJ, Scholpp S (2022). The scaffolding protein Flot2 regulates cytoneme-based transport of Wnt3 in gastric cancer. Abstract.

Rogers S, Scholpp S (2022). Vertebrate Wnt5a – at the crossroads of cellular signalling. Seminars in Cell & Developmental Biology, 125, 3-10.

2021

Winter MJ, Ono Y, Ball JS, Walentinsson A, Michaelsson E, Tochwin A, Scholpp S, Tyler CR, Rees S, Hetheridge MJ, et al (2021). A combined human in silico and CRISPR/Cas9-mediated in vivo zebrafish based approach for supporting gene target validation in early drug discovery.

AbstractThe clinical heterogeneity of heart failure has challenged our understanding of the underlying genetic mechanisms of this disease. In this respect, large-scale patient DNA sequencing studies have become an invaluable strategy for identifying potential genetic contributing factors. The complex aetiology of heart failure, however, also means that in vivo models are vital to understand the links between genetic perturbations and functional impacts. Traditional approaches (e.g. genetically-modified mice) are optimal for assessing small numbers of proposed target genes, but less practical when multiple targets are identified. The zebrafish, in contrast, offers great potential for higher throughput in vivo gene functional assessment to aid target prioritisation and support definitive studies undertaken in mice. Here we used whole-exome sequencing and bioinformatics on human patient data to identify 3 genes (API5, HSPB7, and LMO2) suggestively associated with heart failure that were also predicted to play a broader role in disease aetiology. The role of these genes in cardiovascular system development and function was then further investigated using in vivo CRISPR/Cas9-mediated gene mutation analysis in zebrafish. We observed multiple impacts in F0 knockout zebrafish embryos (crispants) following effective somatic mutation, including reductions in ventricle size, pericardial oedema, and chamber malformation. In the case of lmo2, there was also a significant impact on cardiovascular function as well as an expected reduction in erythropoiesis. The data generated from both the human in silico and zebrafish in vivo assessments undertaken supports roles for API5, HSPB7, and LMO2 in human cardiovascular disease and identifies them as potential drug targets for further investigation. The data presented also supports the use of human in silico genetic variant analysis, in combination with zebrafish crispant phenotyping, as a powerful approach for assessing gene function as part of an integrated multi-level drug target validation strategy.

Abstract.

Rogers S, Scholpp S (2021). Preserving Cytonemes for Immunocytochemistry of Cultured Adherent Cells. In (Ed) , 183-190. Abstract. Author URL.

Sutton G, Kelsh RN, Scholpp S (2021). Review: the Role of Wnt/β-Catenin Signalling in Neural Crest Development in Zebrafish. Frontiers in Cell and Developmental Biology, 9 Abstract.

2020

Cavallo JC, Scholpp S, Flegg MB (2020). Delay-driven oscillations via Axin2 feedback in the Wnt/β-catenin signalling pathway. J Theor Biol, 507

Abstract. Author URL.

Scholpp S (2020). Introduction: in vivo cell biology in zebrafish. Histochem Cell Biol, 154(5), 457-461. Author URL.

Brunt L, Greicius G, Evans BD, Virshup DM, Wedgwood KCA, Scholpp S (2020). Vangl2 regulates the dynamics of Wnt cytonemes in vertebrates. Abstract.

Porter L (2020). Wnt signalling and peroxisome dynamics in the zebrafish (Danio rerio). Abstract.

2019

Zhang C, Scholpp S (2019). Cytonemes in development. Current Opinion in Genetics and Development, 57, 25-30. Abstract.

Routledge D, Scholpp S (2019). Mechanisms of intercellular Wnt transport. Development, 146(10). Abstract. Author URL.

2018

Mattes B, Scholpp S (2018). Emerging role of contact-mediated cell communication in tissue development and diseases. Histochemistry and Cell Biology, 150, 431-442. Abstract.

Liu T-L, Upadhyayula S, Milkie DE, Singh V, Wang K, Swinburne IA, Mosaliganti KR, Collins ZM, Hiscock TW, Shea J, et al (2018). Observing the Cell in its Native State: Imaging Subcellular Dynamics in Multicellular Organisms.

Bosze B, Mattes B, Sinner C, Stricker K, Gourain V, Thumberger T, Tlili S, Weber S, Wittbrodt J, Saunders TE, et al (2018). Pcdh18a-positive tip cells instruct notochord formation in zebrafish.

Brunt L, Scholpp S (2018). The function of endocytosis in Wnt signaling. Cellular and Molecular Life Sciences, 75(5), 785-795. Abstract.

Scholpp S (2018). Wnt/PCP controls spreading of Wnt/β-catenin signals by cytonemes in vertebrates. eLife

2017

Mattes B, Scholpp S (2017). Towards deciphering the molecular mechanism regulating Wnt ligand trafficking. Author URL.

2016

Reinartz I, Sinner C, Stanganello E, Mattes B, Scholpp S, Schug A (2016). 3D Simulations of Morphogen Transport in an Early Fish Embryo. Author URL.

Sinner C, Reinartz I, Boesze B, Scholpp S, Schug A (2016). Dynamic Simulations of Cell Migration with Applications to Brain Development. Author URL.

Stanganello E, Scholpp S (2016). Role of cytonemes in Wnt transport. J Cell Sci, 129(4), 665-672. Abstract. Author URL.

2015

2014

Hagemann AIH, Kurz J, Kauffeld S, Chen Q, Reeves PM, Weber S, Schindler S, Davidson G, Kirchhausen T, Scholpp S, et al (2014). Correction to in vivo analysis of formation and endocytosis of the Wnt/β-Catenin signaling complex in zebrafish embryos [J. Cell Sci. 127, (2014) 3970-3982]. Journal of Cell Science, 127(24).

Rengarajan C, Matzke A, Reiner L, Orian-Rousseau V, Scholpp S (2014). Endocytosis of Fgf8 is a double-stage process and regulates spreading and signaling. PLoS One, 9(1). Abstract. Author URL.

Hagemann AIH, Kurz J, Kauffeld S, Chen Q, Reeves PM, Weber S, Schindler S, Davidson G, Kirchhausen T, Scholpp S, et al (2014). In vivo analysis of formation and endocytosis of the Wnt/β-catenin signaling complex in zebrafish embryos. J Cell Sci, 127(Pt 18), 3970-3982. Abstract. Author URL.

Abstract. Author URL.

2013

Scholpp S, Poggi L, Zigman M (2013). Brain on the stage - spotlight on nervous system development in zebrafish: EMBO practical course, KIT, Sept. 2013. Abstract. Author URL.

Scholpp S, Shimogori T (2013). Building the gateway to consciousness-about the development of the thalamus. In (Ed) . Author URL.

Schmidt R, Strähle U, Scholpp S (2013). Neurogenesis in zebrafish - from embryo to adult. Neural Dev, 8 Abstract. Author URL.

2012

Hagemann AIH, Scholpp S (2012). The Tale of the Three Brothers - Shh, Wnt, and Fgf during Development of the Thalamus. Front Neurosci, 6 Abstract. Author URL.

2011

2010

Scholpp S, Lumsden A (2010). Building a bridal chamber: development of the thalamus. Trends Neurosci, 33(8), 373-380. Abstract. Author URL.

Peukert D, Scholpp S (2010). Ontogenesis of the brain: the development of the thalamus - the gateway to consciousness. BioSpektrum, 16(6), 639-643. Abstract.

Hagemann AI, Schindler S, Scholpp S (2010). The clathrin adaptor-protein subunit ap2m1 regulates canonical Wnt signalling in early neural development of the zebrafish. Author URL.

2009

Scholpp S, Brand M (2009). Neural Patterning: Midbrain-Hindbrain Boundary. In (Ed) Encyclopedia of Neuroscience, 205-211. Abstract.

2008

Scholpp S (2008). Hedgehogs, Fluorescence Imaging & Brain Development. infocus Magazine, 66-75.

2007

2006

2004

Scholpp S, Brand M (2004). Endocytosis controls spreading and effective signaling range of Fgf8 protein. Curr Biol, 14(20), 1834-1841. Abstract. Author URL.

Heinze KG, Schlopp S, Brand M, Schwille P (2004). Probing intercellular pathways and propagation of Fgf8 signalling protein during embryogenesis by FCS. Author URL.

2003

Scholpp S, Brand M (2003). Endocytosis controls propagation of Fgf8 during zebrafish embryogenesis. Author URL.

Scholpp S, Lohs C, Brand M (2003). Engrailed and Fgf8 act synergistically to maintain the boundary between diencephalon and mesencephalon. Development, 130(20), 4881-4893.

Abstract. Author URL.

Scholpp S, Lohs C, Brand M (2003). Erratum: Engrailed and Fgf8 act synergistically to maintain the boundary between diencephalon and mesencephalon (Development vol. 130 (4881-4893)). Development, 130(21).

2002

Abstract. Author URL.

2001

Steffen_Scholpp Details from cache as at 2023-12-06 16:44:11

Refresh publications

External Engagement and Impact

Administrative responsibilities

Chair of the LSI Lab Management Group (LMG)
Deputy Director of Postgraduate Research (D-DPGR)

Committee/panel activities

Panel member of the BBSRC committee C (since 2022)
Panel member of the Polish RC committee, National Science Centre, Poland (since 2019)

Editorial responsibilities

Scientific editor of Mechanisms of Development (MOD) (2016 - present)
Scientific editor of Genesis, John Wiley and Sons, Inc (2015 - present)
Associated editor of Frontiers in Neuroscience (2011 - present)

External doctoral examining nationally and internationally

PhD Maastricht, The Netherlands; Supervisor Dr Stefan Giiselbrecht, 2022
PhD Francis Crick, UK; Supervisor Prof Jim Smith, 2021
PhD iBV, Nice U, France; Supervisor Dr M. Fürthauer, 2021
PhD U Nottingham, UK; Supervisor Prof Martin Gehring, 2019
PhD Oxford Brookes U., UK; Supervisor Prof Alistair McGregor, 2019
MPhil U Bristol, UK; Supervisor Dr Beck Richardson, 2018

Invited lectures

Number of invited lectures in total	International lectures	National lectures
over 60	over 40	over 20

Workshops/Conferences organised

2022 Organizer, EMBO workshop on "Long-distance cell-cell communication", Exeter, UK.

2020 Organizer, Southwest Zebrafish Meeting 2020, Exeter, UK.

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.

Happy Lab Citizen

Teaching

I have taught at the undergraduate and graduate level, including general biology, cell biology, developmental biology, and neurobiology at the Karlsruhe Institute of Technology and the University of Exeter. I have also personally trained over 20 undergraduates in research, some of whom have been my co-authors on peer-reviewed publications.

Teaching is a privilege, and so I try to practice teaching the most effective way to optimize student learning. I enjoy training students to learn science by doing science, both in terms of hands-on research activities and courses that emphasize formulating research questions, critical analysis of data, and drawing meaningful conclusions. My goal is to teach the subject matter, but also to teach students how to train themselves to learn. As module coordinator, I emphasize organization and context while being mindful of how different students learn and what techniques work best both inside and outside of contact hours, in the classroom or the lab.

I have received several teaching awards at the Karlsruhe Institute of Technology, including the German Certificate for Higher Education (Baden-Württemberg Zertifikat fur Hochschuldidaktik, 200h) in 2012. In 2013, I was awarded the Certificate for Academic Leadership (3y, 160h) to guide working groups in an efficient and target-orientated way.

Modules

2023/24

BIO2088 - Advanced Cell Biology

The Scholpp lab in 2020

Supervision / Group

Postdoctoral researchers

Dr Lucy Brunt BBSRC funded
Dr Yosuke Ono BBSRC funded
Dr Tom Piers BRACE funded

Postgraduate researchers

Emma Cooper BBSRC SWBio
Michael Dawes BBSRC SWBio
Kevin Fang Chinese Scholarship Council, CSC
Gemma Sutton BBSRC SWBio

Research Technicians

Ashish Bhandari BBSRC funded
Dr Kelly Sanders BBSRC funded

Alumni

Dr Bernadett Boesze PhD student, DFG funded (2012-2016)
Joshua Donnelly PhD Student (2020-2022)
Holly Elson Technician, MRC funded (2019-2020)
Dr Simone Geyer PhD student, KIT funded (2012-2015)
Dr Anja Hagemann PostDoc, DFG funded (2009-2014)
Agnieszka Kaczmar Technician (2020-2022)
Dr Benjamin Mattes PhD student, Boehringer-Inglelheim funded, (2015-2018)
Dr Daniela Peukert PhD student (2008-2011)
Lauren Porter MSc student(2018-2019)
Dr Charanya Rengarajan PhD student, DFG funded, (2009-2013)
Dr Sally Rogers Postdoc, MRC funded (2019-2022)
Daniel Routledge (MRC DTP Student)
Simone Schindler Technician, BBSRC funded (2017-2018)
Dr Eliana Stanganello PhD student, DFG funded, summa cum laude (2011-2015)
Dr Joana Viana PostDoc, MRC funded (2018-2019)
Dr Chengting Zhang PhD Student, CSC funded (2019-2022)

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Profile

Professor Steffen Scholpp

Professor of Cell and Developmental Biology

Overview

Qualifications

Career

Links

Research

Research interests

Research projects

OPEN POSITIONS:

We're recruiting talented graduates from all areas of bioscience to become MSc students, PhD students and postdoctoral researchers in our lab. Contact us to talk about possibilities.

Join our team!

Research grants

Publications

Key publications

Abstract:Cancer-associated fibroblasts influence Wnt/PCP signaling in gastric cancer cells by cytoneme-based dissemination of ROR2

Abstract:The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer

Abstract:Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling.

Abstract:Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish

Publications by category

Journal articles

Abstract:Cancer-associated fibroblasts influence Wnt/PCP signaling in gastric cancer cells by cytoneme-based dissemination of ROR2

Abstract:The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer

Abstract:Review: the Role of Wnt/β-Catenin Signalling in Neural Crest Development in Zebrafish

Abstract:Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling.

Abstract:Delay-driven oscillations via Axin2 feedback in the Wnt/β-catenin signalling pathway.

Abstract:Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish

Abstract:Vangl2 regulates the dynamics of Wnt cytonemes in vertebrates

Abstract:Cytonemes in development

Abstract:Mechanisms of intercellular Wnt transport.

Abstract:Emerging role of contact-mediated cell communication in tissue development and diseases

Abstract:The function of endocytosis in Wnt signaling

Abstract:Role of cytonemes in Wnt transport.

Abstract:Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation.

Abstract:Filopodia-based Wnt transport during vertebrate tissue patterning.

Abstract:Photolithographic patterning of 3D-formed polycarbonate films for targeted cell guiding.

Abstract:Endocytosis of Fgf8 is a double-stage process and regulates spreading and signaling.

Abstract:In vivo analysis of formation and endocytosis of the Wnt/β-catenin signaling complex in zebrafish embryos.

Abstract:Pax6 regulates the formation of the habenular nuclei by controlling the temporospatial expression of Shh in the diencephalon in vertebrates.

Abstract:Tyrosine phosphorylation of LRP6 by Src and Fer inhibits Wnt/β-catenin signalling.

Abstract:Micropatterned superhydrophobic structures for the simultaneous culture of multiple cell types and the study of cell-cell communication.

Abstract:Neurogenesis in zebrafish - from embryo to adult.

Abstract:The Tale of the Three Brothers - Shh, Wnt, and Fgf during Development of the Thalamus.

Abstract:Wnt3 and Wnt3a are required for induction of the mid-diencephalic organizer in the caudal forebrain.

Abstract:Lhx2 and Lhx9 determine neuronal differentiation and compartition in the caudal forebrain by regulating Wnt signaling.

Abstract:Building a bridal chamber: development of the thalamus.

Abstract:Ontogenesis of the brain: the development of the thalamus - the gateway to consciousness

Abstract:Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway.

Abstract:Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules.

Abstract:Her6 regulates the neurogenetic gradient and neuronal identity in the thalamus.

Abstract:Early developmental specification of the thyroid gland depends on han-expressing surrounding tissue and on FGF signals.

Abstract:Otx1l, Otx2 and Irx1b establish and position the ZLI in the diencephalon.

Abstract:Pbx proteins cooperate with Engrailed to pattern the midbrain-hindbrain and diencephalic-mesencephalic boundaries.

Abstract:Hedgehog signalling from the zona limitans intrathalamica orchestrates patterning of the zebrafish diencephalon.

Abstract:Endocytosis controls spreading and effective signaling range of Fgf8 protein.

Abstract:Zebrafish fgfr1 is a member of the fgf8 synexpression group and is required for fgf8 signalling at the midbrain-hindbrain boundary.

Abstract:Engrailed and Fgf8 act synergistically to maintain the boundary between diencephalon and mesencephalon.

Abstract:Integrity of the midbrain region is required to maintain the diencephalic-mesencephalic boundary in zebrafish no isthmus/pax2.1 mutants.

Abstract:A novel positive transcriptional feedback loop in midbrain-hindbrain boundary development is revealed through analysis of the zebrafish pax2.1 promoter in transgenic lines.

Chapters

Abstract:Preserving Cytonemes for Immunocytochemistry of Cultured Adherent Cells.

Abstract:Neural Patterning: Midbrain-Hindbrain Boundary

Conferences

Reports

Abstract:Brain on the stage - spotlight on nervous system development in zebrafish: EMBO practical course, KIT, Sept. 2013.

Abstract:Molecular pathways controlling development of thalamus and hypothalamus: from neural specification to circuit formation.

Publications by year

In Press

2023

Abstract:Cancer-associated fibroblasts influence Wnt/PCP signaling in gastric cancer cells by cytoneme-based dissemination of ROR2

Abstract:Wnt-7a-positive dendritic cytonemes induce synaptogenesis in cortical neurons

2022

Abstract:Cytoneme-mediated transport of active Wnt5b/Ror2 complexes in zebrafish

Abstract:Extracellular trafficking of Wnt signals in gastric cancer

Abstract:The scaffolding protein Flot2 regulates cytoneme-based transport of Wnt3 in gastric cancer

Abstract:The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer

2021

Abstract:A combined human in silico and CRISPR/Cas9-mediated in vivo zebrafish based approach for supporting gene target validation in early drug discovery

Abstract:Preserving Cytonemes for Immunocytochemistry of Cultured Adherent Cells.

Abstract:
Cancer-associated fibroblasts influence Wnt/PCP signaling in gastric cancer cells by cytoneme-based dissemination of ROR2

Abstract:
The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer

Abstract:
Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling.

Abstract:
Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish

Abstract:
Cancer-associated fibroblasts influence Wnt/PCP signaling in gastric cancer cells by cytoneme-based dissemination of ROR2

Abstract:
The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer

Abstract:
Review: the Role of Wnt/β-Catenin Signalling in Neural Crest Development in Zebrafish

Abstract:
Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling.

Abstract:
Delay-driven oscillations via Axin2 feedback in the Wnt/β-catenin signalling pathway.

Abstract:
Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish

Abstract:
Vangl2 regulates the dynamics of Wnt cytonemes in vertebrates

Abstract:
Cytonemes in development

Abstract:
Mechanisms of intercellular Wnt transport.

Abstract:
Emerging role of contact-mediated cell communication in tissue development and diseases

Abstract:
The function of endocytosis in Wnt signaling

Abstract:
Role of cytonemes in Wnt transport.

Abstract:
Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation.

Abstract:
Filopodia-based Wnt transport during vertebrate tissue patterning.

Abstract:
Photolithographic patterning of 3D-formed polycarbonate films for targeted cell guiding.

Abstract:
Endocytosis of Fgf8 is a double-stage process and regulates spreading and signaling.

Abstract:
In vivo analysis of formation and endocytosis of the Wnt/β-catenin signaling complex in zebrafish embryos.

Abstract:
Pax6 regulates the formation of the habenular nuclei by controlling the temporospatial expression of Shh in the diencephalon in vertebrates.

Abstract:
Tyrosine phosphorylation of LRP6 by Src and Fer inhibits Wnt/β-catenin signalling.

Abstract:
Micropatterned superhydrophobic structures for the simultaneous culture of multiple cell types and the study of cell-cell communication.

Abstract:
Neurogenesis in zebrafish - from embryo to adult.

Abstract:
The Tale of the Three Brothers - Shh, Wnt, and Fgf during Development of the Thalamus.

Abstract:
Wnt3 and Wnt3a are required for induction of the mid-diencephalic organizer in the caudal forebrain.

Abstract:
Lhx2 and Lhx9 determine neuronal differentiation and compartition in the caudal forebrain by regulating Wnt signaling.

Abstract:
Building a bridal chamber: development of the thalamus.

Abstract:
Ontogenesis of the brain: the development of the thalamus - the gateway to consciousness

Abstract:
Zebrafish atlastin controls motility and spinal motor axon architecture via inhibition of the BMP pathway.

Abstract:
Fgf8 morphogen gradient forms by a source-sink mechanism with freely diffusing molecules.

Abstract:
Her6 regulates the neurogenetic gradient and neuronal identity in the thalamus.

Abstract:
Early developmental specification of the thyroid gland depends on han-expressing surrounding tissue and on FGF signals.

Abstract:
Otx1l, Otx2 and Irx1b establish and position the ZLI in the diencephalon.

Abstract:
Pbx proteins cooperate with Engrailed to pattern the midbrain-hindbrain and diencephalic-mesencephalic boundaries.

Abstract:
Hedgehog signalling from the zona limitans intrathalamica orchestrates patterning of the zebrafish diencephalon.

Abstract:
Endocytosis controls spreading and effective signaling range of Fgf8 protein.

Abstract:
Zebrafish fgfr1 is a member of the fgf8 synexpression group and is required for fgf8 signalling at the midbrain-hindbrain boundary.

Abstract:
Engrailed and Fgf8 act synergistically to maintain the boundary between diencephalon and mesencephalon.

Abstract:
Integrity of the midbrain region is required to maintain the diencephalic-mesencephalic boundary in zebrafish no isthmus/pax2.1 mutants.

Abstract:
A novel positive transcriptional feedback loop in midbrain-hindbrain boundary development is revealed through analysis of the zebrafish pax2.1 promoter in transgenic lines.

Abstract:
Preserving Cytonemes for Immunocytochemistry of Cultured Adherent Cells.

Abstract:
Neural Patterning: Midbrain-Hindbrain Boundary

Abstract:
Brain on the stage - spotlight on nervous system development in zebrafish: EMBO practical course, KIT, Sept. 2013.

Abstract:
Molecular pathways controlling development of thalamus and hypothalamus: from neural specification to circuit formation.

Abstract:
Cancer-associated fibroblasts influence Wnt/PCP signaling in gastric cancer cells by cytoneme-based dissemination of ROR2

Abstract:
Wnt-7a-positive dendritic cytonemes induce synaptogenesis in cortical neurons

Abstract:
Cytoneme-mediated transport of active Wnt5b/Ror2 complexes in zebrafish

Abstract:
Extracellular trafficking of Wnt signals in gastric cancer

Abstract:
The scaffolding protein Flot2 regulates cytoneme-based transport of Wnt3 in gastric cancer

Abstract:
The scaffolding protein flot2 promotes cytoneme-based transport of wnt3 in gastric cancer

Abstract:
A combined human in silico and CRISPR/Cas9-mediated in vivo zebrafish based approach for supporting gene target validation in early drug discovery

Abstract:
Preserving Cytonemes for Immunocytochemistry of Cultured Adherent Cells.

Abstract:
Review: the Role of Wnt/β-Catenin Signalling in Neural Crest Development in Zebrafish

Abstract:
Vangl2 promotes the formation of long cytonemes to enable distant Wnt/β-catenin signaling.

Abstract:
Delay-driven oscillations via Axin2 feedback in the Wnt/β-catenin signalling pathway.

Abstract:
Pcdh18a regulates endocytosis of E-cadherin during axial mesoderm development in zebrafish

Abstract:
Vangl2 regulates the dynamics of Wnt cytonemes in vertebrates

Abstract:
Wnt signalling and peroxisome dynamics in the zebrafish (Danio rerio)

Abstract:
Cytonemes in development

Abstract:
Mechanisms of intercellular Wnt transport.

Abstract:
Emerging role of contact-mediated cell communication in tissue development and diseases

Abstract:
The function of endocytosis in Wnt signaling

Abstract:
Role of cytonemes in Wnt transport.

Abstract:
Secreted Frizzled-related Protein 2 (sFRP2) Redirects Non-canonical Wnt Signaling from Fz7 to Ror2 during Vertebrate Gastrulation.

Abstract:
Filopodia-based Wnt transport during vertebrate tissue patterning.

Abstract:
Photolithographic patterning of 3D-formed polycarbonate films for targeted cell guiding.

Abstract:
Endocytosis of Fgf8 is a double-stage process and regulates spreading and signaling.

Abstract:
In vivo analysis of formation and endocytosis of the Wnt/β-catenin signaling complex in zebrafish embryos.

Abstract:
Pax6 regulates the formation of the habenular nuclei by controlling the temporospatial expression of Shh in the diencephalon in vertebrates.

Abstract:
Tyrosine phosphorylation of LRP6 by Src and Fer inhibits Wnt/β-catenin signalling.

Abstract:
Brain on the stage - spotlight on nervous system development in zebrafish: EMBO practical course, KIT, Sept. 2013.

Abstract:
Micropatterned superhydrophobic structures for the simultaneous culture of multiple cell types and the study of cell-cell communication.

Abstract:
Neurogenesis in zebrafish - from embryo to adult.

Abstract:
The Tale of the Three Brothers - Shh, Wnt, and Fgf during Development of the Thalamus.

Abstract:
Wnt3 and Wnt3a are required for induction of the mid-diencephalic organizer in the caudal forebrain.

Abstract:
Lhx2 and Lhx9 determine neuronal differentiation and compartition in the caudal forebrain by regulating Wnt signaling.

Abstract:
Building a bridal chamber: development of the thalamus.

Abstract:
Molecular pathways controlling development of thalamus and hypothalamus: from neural specification to circuit formation.