scholarly journals Trynity controls epidermal barrier function and respiratory tube maturation in Drosophila by modulating apical extracellular matrix nano-patterning

2018 ◽  
Author(s):  
Yuki Itakura ◽  
Sachi Inagaki ◽  
Housei Wada ◽  
Shigeo Hayashi
Keyword(s):  
Extracellular Matrix ◽  
Barrier Function ◽  
Essential Gene ◽  
Epidermal Barrier ◽  
Summary Statement ◽  
Domain Protein ◽  
And Function ◽  
Envelope Layer ◽  
Nano Patterning

AbstractThe outer surface of insects is covered by the cuticle, which is derived from the apical extracellular matrix (aECM). The aECM is secreted by epidermal cells during embryogenesis. The aECM exhibits large variations in structure, function, and constituent molecules, reflecting the enormous diversity in insect appearances. To investigate the molecular principles of aECM organization and function, here we studied the role of a conserved aECM protein, the ZP domain protein Trynity, in Drosophila melanogaster. We first identified trynity as an essential gene for epidermal barrier function. trynity mutation caused disintegration of the outermost envelope layer of the cuticle, resulting in small- molecule leakage and in growth and molting defects. In addition, the tracheal tubules of trynity mutants showed defects in pore-like structures of the cuticle, and the mutant tracheal cells failed to absorb luminal proteins and liquid. Our findings indicated that trynity plays essential roles in organizing nano-level structures in the envelope layer of the cuticle that both restrict molecular trafficking through the epidermis and promote the massive absorption pulse in the trachea.Summary StatementThe zona pellucida domain protein Trynity controls the structural organization and function of the apical extracellular matrix in the epidermis and trachea of Drosophila.

The extracellular matrix of the developing cornea: diversity, deposition and function*

Development ◽  
1988 ◽  
Vol 103 (Supplement) ◽  
pp. 195-205
Author(s):  
J. B. L. Bard ◽  
M. K. Bansal ◽  
A. S. A. Ross
Keyword(s):  
Extracellular Matrix ◽  
Chondroitin Sulphate ◽  
Corneal Stroma ◽  
Experimental System ◽  
Collagen I ◽  
And Function ◽  
20 Nm

This paper examines the role of the extracellular matrix (ECM) in the development of the cornea. After a brief summary of the corneal structure and ECM, we describe evidence suggesting that the differentiation of neural crest (NC) cells into endothelium and fibroblasts is under the control of ocular ECM. We then examine the role of collagen I in stromal morphogenesis by comparing normal corneas with those of homozygous Movl3 mice which do not make collagen I. We report that, in spite of this absence, the cellular morphology of the Movl3 eye is indistinguishable from that of the wild type. In the 16-day mutant stroma, however, the remaining collagens form small amounts of disorganized, thin fibrils rather than orthogonally organized 20 nm-diameter fibrils; a result implying that collagen I plays only a structural role and that its absence is not compensated for. It also suggests that, because these remaining collagens will not form the normal fibrils that they will in vitro, fibrillogenesis in the corneal stroma differs from that elsewhere. The latter part of the paper describes our current work on chick stromal deposition using corneal epithelia isolated with an intact basal lamina that lay down in vitro ∼3μm-thick stromas of organized fibrils similar to that seen in vivo. This experimental system has yielded two unexpected results. First, the amount of collagen and proteoglycans produced by such epithelia is not dependent on whether its substratum is collagenous and we therefore conclude that stromal production by the intact epithelium is more autonomous than hitherto thought. Second, chondroitin sulphate (CS), the predominant proteoglycan, appears to play no role in stromal morphogenesis: epithelia cultured in testicular hyaluronidase, which degrades CS, lay down stromas whose organization and fibrildiameter distribution are indistinguishable from controls. One possible role for CS, however, is as a lubricant which facilitates corneal growth: it could allow fibrils to move over one another without deforming their orthogonal organization. Finally, we have examined the processes of fibrillogenesis in the corneal stroma and conclude that they are different from those elsewhere in the embryo and in vitro, perhaps because there is in the primary stroma an unidentified, highly hydrated ECM macromolecule that embeds the fibrils and that may mediate their morphogenesis.

Establishing the role of PLVAP in protein-losing enteropathy: a homozygous missense variant leads to an attenuated phenotype

2018 ◽  
Vol 55 (11) ◽  
pp. 779-784 ◽  
Author(s):  
Alina Kurolap ◽  
Orly Eshach-Adiv ◽  
Claudia Gonzaga-Jauregui ◽  
Katya Dolnikov ◽  
Adi Mory ◽  
...  
Keyword(s):  
Barrier Function ◽  
Protein Function ◽  
Transmembrane Domain ◽  
Autosomal Recessive Inheritance ◽  
Missense Variant ◽  
Protein Loss ◽  
Protein Losing Enteropathy ◽  
Family Based ◽  
And Function

BackgroundIntestinal integrity is essential for proper nutrient absorption and tissue homeostasis, with damage leading to enteric protein loss, that is, protein-losing enteropathy (PLE). Recently, homozygous nonsense variants in the plasmalemma vesicle-associated protein gene (PLVAP) were reported in two patients with severe congenital PLE. PLVAP is the building block of endothelial cell (EC) fenestral diaphragms; its importance in barrier function is supported by mouse models of Plvap deficiency.ObjectiveTo genetically diagnose two first-degree cousins once removed, who presented with PLE at ages 22 and 2.5 years.MethodsFamily-based whole exome sequencing was performed based on an autosomal recessive inheritance model. In silico analyses were used to predict variant impact on protein structure and function.ResultsWe identified a rare homozygous variant (NM_031310.2:c.101T>C;p.Leu34Pro) in PLVAP, which co-segregated with the disease. Leu34 is predicted to be located in a highly conserved, hydrophobic, α-helical region within the protein’s transmembrane domain, suggesting Leu34Pro is likely to disrupt protein function and/or structure. Electron microscopy and PLVAP immunohistochemistry demonstrated apparently normal diaphragm morphology, predicted to be functionally affected.ConclusionsBiallelic missense variants in PLVAP can cause an attenuated form of the PLE and hypertriglyceridaemia syndrome. Our findings support the role of PLVAP in the pathophysiology of PLE, expand the phenotypic and mutation spectrums and underscore PLVAP’s importance in EC barrier function in the gut.

scholarly journals The Nlrp6 inflammasome is not required for baseline colonic inner mucus layer formation or function

2019 ◽  
Vol 216 (11) ◽  
pp. 2602-2618 ◽  
Author(s):  
Joana K. Volk ◽  
Elisabeth E.L. Nyström ◽  
Sjoerd van der Post ◽  
Beatriz M. Abad ◽  
Bjoern O. Schroeder ◽  
...  
Keyword(s):  
Barrier Function ◽  
Independent Effect ◽  
Mucus Layer ◽  
Effect Analysis ◽  
Innate Immune Signaling ◽  
Inflammatory Bowel ◽  
And Function ◽  
Deficient Mice ◽  
Inflammasome Activity

The inner mucus layer (IML) is a critical barrier that protects the colonic epithelium from luminal threats and inflammatory bowel disease. Innate immune signaling is thought to regulate IML formation via goblet cell Nlrp6 inflammasome activity that controls secretion of the mucus structural component Muc2. We report that isolated colonic goblet cells express components of several inflammasomes; however, analysis of IML properties in multiple inflammasome-deficient mice, including littermate-controlled Nlrp6−/−, detect a functional IML barrier in all strains. Analysis of mice lacking inflammasome substrate cytokines identifies a defective IML in Il18−/− mice, but this phenotype is ultimately traced to a microbiota-driven, Il18-independent effect. Analysis of phenotypic transfer between IML-deficient and IML-intact mice finds that the Bacteroidales family S24-7 (Muribaculaceae) and genus Adlercrutzia consistently positively covary with IML barrier function. Together, our results demonstrate that baseline IML formation and function is independent of inflammasome activity and highlights the role of the microbiota in determining IML barrier function.

scholarly journals Hemicentin-1 is an essential extracellular matrix component of the dermal–epidermal and myotendinous junctions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniela Welcker ◽  
Cornelia Stein ◽  
Natalia Martins Feitosa ◽  
Joy Armistead ◽  
Jin-Li Zhang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Developmental Stages ◽  
Cell Types ◽  
Connective Tissues ◽  
Functional Behavior ◽  
Transmission Electron ◽  
Cellular Microenvironments ◽  
And Function ◽  
Myotendinous Junctions

AbstractThe extracellular matrix architecture is composed of supramolecular fibrillar networks that define tissue specific cellular microenvironments. Hemicentins (Hmcn1 and Hmcn2) are ancient and very large members (> 600 kDa) of the fibulin family, whose short members are known to guide proper morphology and functional behavior of specialized cell types predominantly in elastic tissues. However, the tissue distribution and function of Hemicentins within the cellular microenvironment of connective tissues has remained largely unknown. Performing in situ hybridization and immunofluorescence analyses, we found that mouse Hmcn1 and Hmcn2 show a complementary distribution throughout different tissues and developmental stages. In postnatal dermal–epidermal junctions (DEJ) and myotendinous junctions (MTJ), Hmcn1 is primarily produced by mesenchymal cells (fibroblasts, tenocytes), Hmcn2 by cells of epithelial origin (keratinocytes, myocytes). Hmcn1−/− mice are viable and show no overt phenotypes in tissue tensile strength and locomotion tests. However, transmission electron microscopy revealed ultrastructural basement membrane (BM) alterations at the DEJ and MTJ of Hmcn1−/− mice, pointing to a thus far unknown role of Hmcn1 for BM and connective tissue boundary integrity.

scholarly journals Tissue-resident macrophages regulate lymphatic vessel growth and patterning in the developing heart

2020 ◽  
Author(s):  
Thomas J. Cahill ◽  
Xin Sun ◽  
Christophe Ravaud ◽  
Cristina Villa del Campo ◽  
Konstantinos Klaourakis ◽  
...  
Keyword(s):  
Heart Development ◽  
Lymphatic Vessel ◽  
Fetal Liver ◽  
Lymphatic Endothelial Cell ◽  
Vascular Plexus ◽  
Developing Heart ◽  
Vessel Growth ◽  
Summary Statement ◽  
And Function

AbstractMacrophages are components of the innate immune system with key roles in tissue inflammation and repair. It is now evident that macrophages also support organogenesis, but few studies have characterized their identity, ontogeny and function during heart development. Here, we show that resident macrophages in the subepicardial compartment of the developing heart coincide with the emergence of new lymphatics and interact closely with the nascent lymphatic capillaries. Consequently, global macrophage-deficiency led to extensive vessel disruption with mutant hearts exhibiting shortened and mis-patterned lymphatics. The origin of cardiac macrophages was linked to the yolk sac and fetal liver. Moreover, Csf1r+ and Cx3cr1+ myeloid sub-lineages were found to play essential functions in the remodeling of the lymphatic endothelium. Mechanistically, macrophage hyaluronan was found to be required for lymphatic sprouting by mediating direct macrophage-lymphatic endothelial cell interactions. Together, these findings reveal insight into the role of macrophages as indispensable mediators of lymphatic growth during the development of the mammalian cardiac vasculature.Summary statementTissue-resident macrophages are indispensable mediators of lymphatic vessel formation during heart development and function to remodel the vascular plexus.

The Caenorhabditis elegans Patched domain protein PTR-4 is required for proper organization of the precuticular apical extracellular matrix

Genetics ◽  
2021 ◽  
Author(s):  
Jennifer D Cohen ◽  
Carla E Cadena del Castillo ◽  
Nicholas D Serra ◽  
Andres Kaech ◽  
Anne Spang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Caenorhabditis Elegans ◽  
Zona Pellucida ◽  
Barrier Function ◽  
Transmembrane Proteins ◽  
Ridge Structure ◽  
Related Family ◽  
Apical Side ◽  
Domain Protein ◽  
Related Proteins

Abstract The Patched-related superfamily of transmembrane proteins can transport lipids or other hydrophobic molecules across cell membranes. While the Hedgehog receptor Patched has been intensively studied, much less is known about the biological roles of other Patched-related family members. Caenorhabditis elegans has a large number of Patched-related proteins, despite lacking a canonical Hedgehog pathway. Here, we show that PTR-4 promotes the assembly of the precuticle apical extracellular matrix, a transient and molecularly distinct matrix that precedes and patterns the later collagenous cuticle or exoskeleton. ptr-4 mutants share many phenotypes with precuticle mutants, including defects in eggshell dissolution, tube shaping, alae (cuticle ridge) structure, molting, and cuticle barrier function. PTR-4 localizes to the apical side of a subset of outward-facing epithelia, in a cyclical manner that peaks when precuticle matrix is present. Finally, PTR-4 is required to limit the accumulation of the lipocalin LPR-3 and to properly localize the Zona Pellucida domain protein LET-653 within the precuticle. We propose that PTR-4 transports lipids or other hydrophobic components that help to organize the precuticle and that the cuticle and molting defects seen in ptr-4 mutants result at least in part from earlier disorganization of the precuticle.

The crosstalk of hyaluronan-based extracellular matrix and synapses

2008 ◽  
Vol 4 (3) ◽  
pp. 249-257 ◽  
Author(s):  
Renato Frischknecht ◽  
Constanze I. Seidenbecher
Keyword(s):  
Extracellular Matrix ◽  
Nervous System ◽  
Hyaluronic Acid ◽  
Chondroitin Sulphate ◽  
Specific Form ◽  
Perineuronal Net ◽  
Chondroitin Sulphate Proteoglycans ◽  
And Function ◽  
Brain Extracellular Space

Many neurons and their synapses are enwrapped in a brain-specific form of the extracellular matrix (ECM), the so-called perineuronal net (PNN). It forms late in the postnatal development around the time when synaptic contacts are stabilized. It is made of glycoproteins and proteoglycans of glial as well as neuronal origin. The major organizing polysaccharide of brain extracellular space is the polymeric carbohydrate hyaluronic acid (HA). It forms the backbone of a meshwork consisting of CNS proteoglycans such as the lectican family of chondroitin sulphate proteoglycans (CSPG). This family comprises four abundant components of brain ECM: aggrecan and versican as broadly expressed CSPGs and neurocan and brevican as nervous-system-specific family members. In this review, we intend to focus on the specific role of the HA-based ECM in synapse development and function.

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