Dorsal-ventral patterning in vertebrate and invertebrate embryos is mediated by a conserved system of secreted proteins that establishes a bone morphogenetic protein (BMP) gradient. Although the Drosophila embryonic Decapentaplegic (Dpp) gradient has served as a model to understand how morphogen gradients are established, no role for the extracellular matrix has been previously described. Here we show that type IV collagen extracellular matrix proteins bind Dpp and regulate its signalling in both the Drosophila embryo and ovary. We provide evidence that the interaction between Dpp and type IV collagen augments Dpp signalling in the embryo by promoting gradient formation, yet it restricts the signalling range in the ovary through sequestration of the Dpp ligand. Together, these results identify a critical function of type IV collagens in modulating Dpp in the extracellular space during Drosophila development. On the basis of our findings that human type IV collagen binds BMP4, we predict that this role of type IV collagens will be conserved.
Recombinant human bone morphogenetic protein 2B stimulates PC12 cell differentiation: potentiation and binding to type IV collagen
Collagen type IV of Drosophila is stockpiled in the growing oocyte and differentially located during early stages of embryogenesis
Drosophila MAD, a member of the Smad family, translocates to the nucleus upon stimulation of the dpp pathway
decapentaplegic is essential for the maintenance and division of germline stem cells in the Drosophila ovary
The L45 loop in type I receptors for TGF-beta family members is a critical determinant in specifying Smad isoform activation
A protein trap strategy to detect GFP-tagged proteins expressed from their endogenous loci in Drosophila
Type IV collagen is transcriptionally regulated by Smad1 under advanced glycation end product (AGE) stimulation.
Integrin-dependent apposition of Drosophila extraembryonic membranes promotes morphogenesis and prevents anoikis
Drosophila Dpp morphogen movement is independent of dynamin-mediated endocytosis but regulated by the glypican members of heparan sulfate proteoglycans
Facilitated transport of a Dpp/Scw heterodimer by Sog/Tsg leads to robust patterning of the Drosophila blastoderm embryo
Molecular recognition in the assembly of collagens: terminal noncollagenous domains are key recognition modules in the formation of triple helical protomers
Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery)
Engineering three-dimensional stem cell morphogenesis for the development of tissue models and scalable regenerative therapeutics
Multistep molecular mechanism for bone morphogenetic protein extracellular transport in the Drosophila embryo
Activin A binds to perlecan through its pro-region that has heparin/heparan sulfate binding activity.
Activation of bone morphogenetic protein 4 signaling leads to glomerulosclerosis that mimics diabetic nephropathy.
The osteoconductivity of biomaterials is regulated by bone morphogenetic protein 2 autocrine loop involving α2β1 integrin and mitogen-activated protein kinase/extracellular related kinase signaling pathways
COL4A1 and COL4A2 mutations and disease: insights into pathogenic mechanisms and potential therapeutic targets
New insights into extracellular and post-translational regulation of TGF-β family signalling pathways
Secreted, receptor-associated bone morphogenetic protein regulators reduce stochastic noise intrinsic to many extracellular morphogen distributions
Extracellular matrix in development: insights from mechanisms conserved between invertebrates and vertebrates
Pericyte recruitment during vasculogenic tube assembly stimulates endothelial basement membrane matrix formation
Smad4-dependent pathways control basement membrane deposition and endodermal cell migration at early stages of mouse development
Model-based analysis for qualitative data: an application in Drosophila germline stem cell regulation
Multiplexin promotes heart but not aorta morphogenesis by polarized enhancement of slit/robo activity at the heart lumen
Analysis of adhesion molecules and basement membrane contributions to synaptic adhesion at the Drosophila embryonic NMJ
Drosophila MMP2 regulates the matrix molecule faulty attraction (Frac) to promote motor axon targeting in Drosophila.
Type IV collagen alpha chains of the basement membrane in the rat bronchioalveolar transitional segment
A review of the effects of the cell environment physicochemical nanoarchitecture on stem cell commitment
Chordin forms a self-organizing morphogen gradient in the extracellular space between ectoderm and mesoderm in the Xenopus embryo
Mechanism of regulation of PPARG expression of mesenchymal stem cells by osteogenesis-mimicking extracellular matrices
Molecular control of capillary morphogenesis and maturation by recognition and remodeling of the extracellular matrix: functional roles of endothelial cells and pericytes in health and disease
Decellularized Extracellular Matrix as an In Vitro Model to Study the Comprehensive Roles of the ECM in Stem Cell Differentiation
Wnt ligands regulate Tkv expression to constrain Dpp activity in the Drosophila ovarian stem cell niche
Synthetic enzyme-substrate tethering obviates the Tolloid-ECM interaction during Drosophila BMP gradient formation
Disruption of transforming growth factor-β superfamily signaling: A shared mechanism underlying hereditary cerebral small vessel disease
Control of germline stem cell differentiation by Polycomb and Trithorax group genes in the niche microenvironment
Collagen XXVIII is a distinctive component of the peripheral nervous system nodes of ranvier and surrounds nonmyelinating glial cells
Regeneration of dental pulp/dentine complex with a three-dimensional and scaffold-free stem-cell sheet-derived pellet
Molecular and Genetic Analyses of Collagen Type IV Mutant Mouse Models of Spontaneous Intracerebral Hemorrhage Identify Mechanisms for Stroke Prevention
Drosophila ML-DmD17-c3 cells respond robustly to Dpp and exhibit complex transcriptional feedback on BMP signaling components
Collagen type IV and Perlecan exhibit dynamic localization in the Allantoic Core Domain, a putative stem cell niche in the murine allantois
A chloride ring is an ancient evolutionary innovation mediating the assembly of the collagen IV scaffold of basement membranes.
The Intersection of Theory and Application in Elucidating Pattern Formation in Developmental Biology
Biological Silicon Stimulates Collagen Type 1 and Osteocalcin Synthesis in Human Osteoblast-Like Cells Through the BMP-2/Smad/RUNX2 Signaling Pathway
Transcriptome analysis during photostimulated recrudescence reveals distinct patterns of gene regulation in Siberian hamster ovaries†.
siRNA-mediated suppression of collagen type iv alpha 2 (COL4A2) mRNA inhibits triple-negative breast cancer cell proliferation and migration
The calcium channel subunit α2 δ-3 organizes synapses via an activity-dependent and autocrine BMP signaling pathway
Genetic interactions between the DBL-1/BMP-like pathway and dpy body size-associated genes in Caenorhabditis elegans
Evolutionary expansion of apical extracellular matrix is required for the elongation of cells in a novel structure.
Position matters: variability in the spatial pattern of BMP modulators generates functional diversity
A nanobody-based toolset to investigate the role of protein localization and dispersal in Drosophila
Discoidin-domain receptor coordinates cell-matrix adhesion and collective polarity in migratory cardiopharyngeal progenitors
Coacting enhancers can have complementary functions within gene regulatory networks and promote canalization
Control of germline stem cell self-renewal and differentiation in the Drosophila ovary: concerted actions of niche signals and intrinsic factors
Extracellular Regulation of Bone Morphogenetic Protein Activity by the Microfibril Component Fibrillin-1.
Laminin and integrin expression in the ventral ectodermal ridge of the mouse embryo: implications for regulation of BMP signalling
The triple helix of collagens - an ancient protein structure that enabled animal multicellularity and tissue evolution
The Gyc76C Receptor Guanylyl Cyclase and the Foraging cGMP-Dependent Kinase Regulate Extracellular Matrix Organization and BMP Signaling in the Developing Wing of Drosophila melanogaster
Maintenance of Proper Germline Stem Cell Number Requires Adipocyte Collagen in Adult Drosophila Females
Smad4-dependent morphogenic signals control the maturation and axonal targeting of basal vomeronasal sensory neurons to the accessory olfactory bulb
Structures of collagen IV globular domains: insight into associated pathologies, folding and network assembly
Neuronal octopamine signaling regulates mating-induced germline stem cell increase in female Drosophila melanogaster.
A new MMP-mediated prodomain cleavage mechanism to activate bone morphogenetic proteins from the extracellular matrix.
Macrophages and Their Organ Locations Shape Each Other in Development and Homeostasis - A Drosophila Perspective.
Transforming Growth Factor β/activin signalling induces epithelial cell flattening during Drosophila oogenesis
Insights into the osteoblast precursor differentiation towards mature osteoblasts induced by continuous BMP-2 signaling
Learning from BMPs and their biophysical extracellular matrix microenvironment for biomaterial design
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