A5041107408- Hedgehog Signaling Pathway Studies
- Proteoglycans and glycosaminoglycans research
- Epigenetics and DNA Methylation
- Fibroblast Growth Factor Research
- Glycosylation and Glycoproteins Research
- Connective tissue disorders research
- Genomics and Chromatin Dynamics
- Developmental Biology and Gene Regulation
- Wnt/β-catenin signaling in development and cancer
- Renal and related cancers
- Hippo pathway signaling and YAP/TAZ
- Carbohydrate Chemistry and Synthesis
- Allergic Rhinitis and Sensitization
- Food Allergy and Anaphylaxis Research
- Cell Adhesion Molecules Research
- Congenital Ear and Nasal Anomalies
- Congenital heart defects research
- Neurogenesis and neuroplasticity mechanisms
- Immunotherapy and Immune Responses
- Plant Reproductive Biology
- Genetic and rare skin diseases.
- Nuclear Structure and Function
- Polysaccharides and Plant Cell Walls
- Lysosomal Storage Disorders Research
- CAR-T cell therapy research
University of Münster
2016-2025
Helmholtz Zentrum München
2013
University Hospital Münster
2011-2012
Institute of Molecular Biotechnology
2010
University of California, San Diego
1999-2005
Olive View-UCLA Medical Center
2002
University of California, Los Angeles
2002
Research Center Borstel - Leibniz Lung Center
1997-1999
Kiel University
1998
We report the cloning and partial characterization of fourth member vertebrate heparan sulfate/heparin: GlcNAc N-deacetylase/GlcNN-sulfotransferase family, which we designate NDST4. Full-length cDNA clones containing entire coding region 872 amino acids were obtained from human mouse libraries. The deduced acid sequence NDST4 showed high identity to NDST1, NDST2, NDST3 in both species. maps chromosome 4q25–26, very close NDST3, located at 4q26–27. These observations, taken together with...
Mutant mice bearing a targeted disruption of the heparan sulfate (HS) modifying enzyme GlcNAc N-deacetylase/N-sulfotransferase 1 (Ndst1) exhibit severe developmental defects forebrain and forebrain-derived structures, including cerebral hypoplasia, lack olfactory bulbs, eye axon guidance errors. Neural crest-derived facial structures are also severely affected. We show that properly synthesized is required for normal development brain face, Ndst1 modifier sulfate-dependent growth...
Directional motility is a fundamental function of immune cells, which are recruited to sites pathogen invasion or tissue damage by chemoattractant signals. To move, cells need generate lamellipodial membrane protrusions at the front and retract trailing end. These elementary events initiated Rho-family GTPases, cycle between active GTP-bound inactive GDP-bound states. How activity these “molecular switches” spatially coordinated only beginning be understood. Here, we show that myosin IXb...
The ectodomains of numerous proteins are released from cells by matrix metalloproteases to yield soluble intercellular regulators. A disintegrin and metalloprotease (ADAM) family members have often been found be the responsible "sheddases," ADAM17/tumor necrosis factor-α-converting enzyme being its best characterized member. In this work, we show that ShhNp (lipidated membrane-tethered Sonic hedgehog) is Bosc23 metalloprotease-mediated ectodomain shedding, resulting in a biologically active...
Heparan sulfate, an extensively sulfated glycosaminoglycan abundant on cell surface proteoglycans, regulates intercellular signaling through its binding to various growth factors and receptors. In the lacrimal gland, branching morphogenesis depends interaction of heparan sulfate with Fgf10-Fgfr2b. To address if gland development FGF 2-O-sulfation uronic acids 6-O-sulfation glucosamine residues, we genetically ablated 2-O 6-O sulfotransferases (Hs2st, Hs6st1, Hs6st2) in developing gland....
ABSTRACT All morphogens of the Hedgehog (Hh) family are synthesized as dual-lipidated proteins, which results in their firm attachment to surface cell they were produced. Thus, Hh release into extracellular space requires accessory protein activities. We suggested previously that proteolytic removal N- and C-terminal lipidated peptides (shedding) could be one such activity. More recently, secreted glycoprotein Scube2 (signal peptide, cubulin domain, epidermal-growth-factor-like 2) was also...
Abstract Although hundreds of cytosolic or transmembrane molecules form the primary cilium, few secreted are known to contribute ciliogenesis. Here, homologous metalloproteases ADAMTS9 and ADAMTS20 identified as ciliogenesis regulators that act intracellularly. Secreted furin-processed bound heparan sulfate was internalized by LRP1, LRP2 clathrin-mediated endocytosis be gathered in Rab11 vesicles with a unique periciliary localization defined super-resolution microscopy. CRISPR-Cas9...
Multiple signaling molecules, including bone morphogenic proteins (BMP) and fibroblast growth factors (FGF), play important roles in early lens development. However, how these morphogens are regulated is still largely unknown. Heparan sulfate participates both morphogen transport morphogen-receptor interaction. In this study, we demonstrate that inactivation of the heparan biosynthetic gene Ndst1 resulted invagination defects disruption lens-determination expression, leading to severe...
Preferential outgrowth of the bud cells forms basis branching morphogenesis. Here, we show that lacrimal gland development requires specific modification heparan sulfates by Ndst genes at tip bud. Systemic and conditional knockout experiments demonstrate tissue requirement Ndst1 Ndst2 in epithelial, but not mesenchymal, cells, functional importance Fgf10-Fgfr2b, Fgf1-Fgfr2b, complex formation. Consistent with this, Fgf10-induced ectopic budding explant cultures is dependent upon gene dose,...
The ependymal multiciliated epithelium in the brain restricts cerebrospinal fluid to cerebral ventricles and regulates its flow. We report here that mice deficient for myosin IXa (Myo9a), an actin-dependent motor molecule with a Rho GTPase-activating (GAP) domain, develop severe hydrocephalus stenosis closure of ventral caudal 3rd ventricle aqueduct. Myo9a is expressed maturing epithelial cells, absence leads impaired maturation cells. deficiency further resulted distorted ependyma due...
Directed migration of stimulated dendritic cells (DCs) to secondary lymphoid organs and their interaction with Ag-specific T is a prerequisite for the induction primary immune responses. In this article, we show that murine DCs lack myosin IXB (Myo9b), motorized negative regulator RhoA signaling, exhibit increased Rho signaling activity downstream acto-myosin contractility, inactivation target protein cofilin, an actin-depolymerizing factor. On functional level, Myo9b(-/-) showed impaired...
Hedgehog (Hh) morphogens are essential regulators of growth and patterning at considerable distances from their source, despite being produced as double lipidated proteins that attach to the outer plasma membrane (PM) leaflet producing cells. While mechanisms overcome this limitation include 12-pass transmembrane protein Dispatched1 (Disp), soluble glycoprotein Scube2, proteolytic processing peptide termini, lipoproteins (LPPs) acting Hh acceptors transporters, molecular interplay these...
Abstract Vascular endothelial growth factor (VEGF), a major regulator of blood vessel formation, is naturally bound to heparan sulfate proteoglycans in the extracellular matrix (ECM). Yet, how physical presentation VEGF by impacts its signaling potential remains fully unknown. To address this question, we have developed tunable heparin-containing hydrogel model that recapitulates natural binding modes with full and independent control over properties. Using model, show degree heparin...
Expansins are a family of proteins that catalyse long‐term extension isolated plant cell walls due to an as yet unknown biochemical mechanism. They divided into two groups, the α‐expansins and β‐expansins, latter group consisting grass I allergens their vegetative homologs. These allergens, which more than 95% patients allergic pollen possess IgE antibodies, highly immunologically crossreactive glycoproteins exclusively expressed in all grasses. Alignments amino‐acid sequences derived from...
Glycosaminoglycans (GAGs) play a central role in embryonic development by regulating the movement and signaling of morphogens. We have previously demonstrated that GAGs are co-receptors for Fgf10 lacrimal gland epithelium, but their function Fgf10-producing periocular mesenchyme is still poorly understood. In this study, we generated mesenchymal ablation UDP-glucose dehydrogenase (Ugdh), an essential biosynthetic enzyme GAGs. Although RNA expressed normally mesenchyme, Ugdh mutation leads to...
RhoA is thought to be essential for coordination of the membrane protrusions and retractions required immune cell motility directed migration. Whether subfamily Rho (Ras homolog) GTPases (RhoA, RhoB, RhoC) actually migration primary cells difficult predict. Macrophages isolated from myeloid-restricted RhoA/RhoB (conditional) double knock-out (dKO) mice did not express RhoC were essentially "pan-Rho"-deficient. Using real-time chemotaxis assays, we found that retraction trailing edge was...
Abstract Decision making in cellular ensembles requires the dynamic release of signaling molecules from producing cells into extracellular compartment. One important example that require regulated order to signal over several cell diameters is Hedgehog (Hh) family, because all Hhs are synthesized as dual-lipidated proteins firmly tether outer membrane leaflet produces them. Factors for vertebrate Hh family member Sonic (Shh) include cell-surface sheddases remove lipidated terminal peptides,...
Abstract Cellular differentiation is directly determined by concentration gradients of morphogens. As a central model for gradient formation during development, Hedgehog (Hh) morphogens spread away from their source to direct growth and pattern in Drosophila wing eye discs. What not known how extracellular Hh achieved it translates into precise gradients. Here we show that two separate binding areas located on opposite sides the molecule can interact simultaneously with heparan sulfate (HS)...
Heparan sulfates (HSs) exert critical regulatory actions on many proteins, including growth factors, and are essential for normal development. Variations in their specific sulfation patterns known to regulate binding signaling of fibroblast factors (FGFs) via tyrosine kinase receptors (FGFRs). We previously reported differences between HS species expressed by embryonic day 10 (E10) E12 mouse neural precursor cells. have examined the abilities different support relevant FGF-FGFR combinations...