scholarly journals The netrin receptor DCC focuses invadopodia-driven basement membrane transmigration in vivo

2013 ◽  
Vol 201 (6) ◽  
pp. 903-913 ◽  
Author(s):  
Elliott J. Hagedorn ◽  
Joshua W. Ziel ◽  
Meghan A. Morrissey ◽  
Lara M. Linden ◽  
Zheng Wang ◽  
...  
Keyword(s):  
Basement Membrane ◽  
Cancer Metastasis ◽  
Normal Development ◽  
Basement Membranes ◽  
Membrane Interface ◽  
Anchor Cell ◽  
Membrane Components ◽  
Invasive Cell ◽  
Basement Membrane Components

Though critical to normal development and cancer metastasis, how cells traverse basement membranes is poorly understood. A central impediment has been the challenge of visualizing invasive cell interactions with basement membrane in vivo. By developing live-cell imaging methods to follow anchor cell (AC) invasion in Caenorhabditis elegans, we identify F-actin–based invadopodia that breach basement membrane. When an invadopodium penetrates basement membrane, it rapidly transitions into a stable invasive process that expands the breach and crosses into the vulval tissue. We find that the netrin receptor UNC-40 (DCC) specifically enriches at the site of basement membrane breach and that activation by UNC-6 (netrin) directs focused F-actin formation, generating the invasive protrusion and the cessation of invadopodia. Using optical highlighting of basement membrane components, we further demonstrate that rather than relying solely on proteolytic dissolution, the AC’s protrusion physically displaces basement membrane. These studies reveal an UNC-40–mediated morphogenetic transition at the cell–basement membrane interface that directs invading cells across basement membrane barriers.

scholarly journals Basement membrane proteoglycans in glomerular morphogenesis: chondroitin sulfate proteoglycan is temporally and spatially restricted during development.

1993 ◽  
Vol 41 (3) ◽  
pp. 401-414 ◽  
Author(s):  
K J McCarthy ◽  
K Bynum ◽  
P L St John ◽  
D R Abrahamson ◽  
J R Couchman
Keyword(s):  
Basement Membrane ◽  
Chondroitin Sulfate ◽  
Basement Membranes ◽  
Chondroitin Sulfate Proteoglycan ◽  
Sulfate Proteoglycan ◽  
Electron Microscopic ◽  
Ureteric Buds ◽  
Membrane Components ◽  
Almost All ◽  
Basement Membrane Components

We previously reported the presence of a basement membrane-specific chondroitin sulfate proteoglycan (BM-CSPG) in basement membranes of almost all adult tissues. However, an exception to this ubiquitous distribution was found in the kidney, where BM-CSPG was absent from the glomerular capillary basement membrane (GBM) but present in other basement membranes of the nephron, including collecting ducts, tubules, Bowman's capsule, and the glomerular mesangium. In light of this unique pattern of distribution and of the complex histoarchitectural reorganization occurring during nephrogenesis, the present study used light and electron microscopic immunohistochemistry to examine the distribution of BM-CSPG and basement membrane heparan sulfate proteoglycan (BM-HSPG) during prenatal and postnatal renal development in the rat. Our results show that the temporal and spatial pattern of expression of BM-CSPG during nephrogenesis is unlike that reported for other basement membrane components such as laminin, fibronectin, and BM-HSPG, all of which can be found in the earliest formed basement membranes of the vesicle-stage nephron. Although BM-CSPG is present in the basement membranes of the invading vasculature and ureteric buds, its first appearance in nephron basement membrane occurs during the late comma stage. In capillary loop-stage glomeruli of prenatal animals, BM-CSPG is present in the presumptive mesangial matrix but undetectable in the GBM. However, as postnatal glomerular maturation progresses BM-CSPG is also found in both the lamina rara interna and lamina densa of the GBM in progressively increasing amounts, being most evident in the GBM of 21-day-old animals. Micrographs of glomeruli from 42-day-old animals show that BM-CSPG gradually disappears from the GBM and, by 56 days after birth, appears to be completely absent from the GBM, its pattern of distribution resembling that of the adult animal. Our results show that BM-CSPG is not required for the initial assembly of basement membranes but may in fact serve to stabilize basement membrane structure after histoarchitectural reorganization is completed.

scholarly journals The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasion in vivo

2021 ◽  
Author(s):  
Jayson J. Smith ◽  
Yutong Xiao ◽  
Nithin Parsan ◽  
Michael A. Q. Martinez ◽  
Frances E. Q. Moore ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromatin Remodeling ◽  
Cell Cycle Progression ◽  
Cancer Metastasis ◽  
Basement Membranes ◽  
Cellular Invasion ◽  
Chromatin Remodeling Complex ◽  
Essential Components ◽  
Anchor Cell

SUMMARYChromatin remodeling complexes, such as the SWItching defective/Sucrose Non-Fermenting (SWI/SNF) ATP-dependent chromatin remodeling complex, coordinate metazoan development through broad regulation of chromatin accessibility and transcription, ensuring normal cell cycle control and cellular differentiation in a lineage-specific and temporally restricted manner. Mutations in subunits of chromatin regulating factors are associated with a variety of diseases and cancer metastasis co-opts cellular invasion found in healthy cells during development. Here we utilize Caenorhabditis elegans anchor cell (AC) invasion as an in vivo model to identify the suite of chromatin and chromatin regulating factors (CRFs) that promote cellular invasiveness. We demonstrate that the SWI/SNF ATP-dependent chromatin remodeling complex is a critical regulator of AC invasion, with pleiotropic effects on both G0/G1 cell cycle arrest and activation of invasive machinery. Using targeted protein degradation and RNA interference (RNAi), we show that SWI/SNF contributes to AC invasion in a dose-dependent fashion, with lower levels of activity in the AC corresponding to aberrant cell cycle entry and increased loss of invasion. Finally, we implicate the SWI/SNF BAF assembly in the regulation of the cell cycle, whereas our data suggests that the SWI/SNF PBAF assembly promotes AC attachment to the basement membrane (BM) and promotes the activation of the invasive machinery. Together these findings demonstrate that the SWI/SNF complex is necessary for two essential components of AC invasion: arresting cell cycle progression and remodeling the BM. The work here provides valuable single-cell mechanistic insight into the contributions of SWI/SNF assembly and subunit-specific disruptions to tumorigenesis and cancer metastasis.SUMMARY STATEMENTCellular invasion through basement membranes by the C. elegans anchor cell requires both BAF- and PBAF SWI/SNF complexes to arrest the cell cycle and promote the expression of pro-invasive genes.

scholarly journals What is Known of the Production of Basement Membrane Components

1983 ◽  
Vol 31 (1A_suppl) ◽  
pp. 159-163 ◽  
Author(s):  
G.W. Laurie ◽  
C.P. Leblond
Keyword(s):  
Golgi Apparatus ◽  
Basement Membrane ◽  
Type Iv Collagen ◽  
Secretory Granules ◽  
Basement Membranes ◽  
Type Iv ◽  
Stage Of Development ◽  
Membrane Components ◽  
Endodermal Cells ◽  
Basement Membrane Components

Immunohistochemistry was used to identify basement membrane components and examine their production by associated cells. Four substances were identified in a series of basement membranes in rats aged 20 days to 34 months, namely, type IV collagen, laminin, heparan sulfate proteoglycan, and fibronectin. They were then all localized to the basal lamina part of basement membranes and, presumably, are integrated within this layer. The production of type IV collagen was first examined in the embryonic endodermal cells associated with Reichert's membrane in the rat parietal yolk sac. The rough endoplasmic reticulum (rER), Golgi apparatus, and putative secretory granules of endodermal cells were immunostained, suggesting that these organelles participated in the biogenesis of type IV collagen. However, in rats aged 20 days or more, the cells associated with basement membranes were usually unstained. An exception was noted in the continually growing incisor tooth where the endothelial cells at the proliferating end usually showed immunostaining of rER and Golgi apparatus. It is, therefore, proposed that the formation of type IV collagen for basement membrane occurs at an early stage of development in the life of producer cells. Little is known of the formation of other basement membrane components during development, but there is immunohistochemical evidence that laminin and fibronectin are produced along the same secretory pathway as type IV collagen.

scholarly journals Deposition of fibronectin and laminin in the basement membrane of the rat parietal yolk sac: immunohistochemical and biosynthetic studies.

1983 ◽  
Vol 96 (1) ◽  
pp. 104-111 ◽  
Author(s):  
P S Amenta ◽  
C C Clark ◽  
A Martinez-Hernandez
Keyword(s):  
Basement Membrane ◽  
Metabolic Labeling ◽  
Membrane Interface ◽  
Maternal Circulation ◽  
Electron Microscopic ◽  
Type Iv ◽  
Reichert's Membrane ◽  
Membrane Components ◽  
Biosynthetic Studies ◽  
Basement Membrane Components

Rat parietal yolk sacs (PYS) at gestational ages 7.5, 9.5, 11.5, 13.5, 14.5, and 16.5 d were reacted with antibodies against laminin or plasma fibronectin. At all times studied, laminin consistently gave a positive reaction with Reichert's membrane and with the cytoplasm of PYS cells. In contrast, fibronectin gave a negative reaction with Reichert's membrane at day 7.5, was weakly positive at day 9.5, and from then on was increasingly positive with maximum reactivity at 14.5 d. By electron microscopic immunohistochemistry, antilaminin reacted strongly with 14.5-d Reichert's membrane and with the contents of the rough endoplasmic reticulum RER cisternae of the PYS cells. Antifibronectin had some spotty reactivity with Reichert's membrane, but the cytoplasm of the PYS cells was negative. The contents of the vitelline vessels and the interface between trophoblast and Reichert's membrane were strongly positive. Metabolic labeling of PYS cells in organ culture clearly demonstrated the presence of laminin, type IV procollagen, and entactin both in the medium and in tissues, but fibronectin was absent. No component in the medium bound to gelatin-Sepharose columns. These studies demonstrate that PYS cells, which actively synthesize and secrete basement membrane components, do not synthesize any detectable fibronectin. Furthermore, the anti-fibronectin staining pattern in the vitelline vessels and trophoblast-Reichert's membrane interface strongly suggests that the fibronectin present in Reichert's membrane is derived from the maternal circulation and is merely "trapped" in the membrane.

scholarly journals The ultrastructural localization of two basement membrane components: entactin and laminin in rat tissues.

1984 ◽  
Vol 32 (3) ◽  
pp. 289-298 ◽  
Author(s):  
A Martinez-Hernandez ◽  
A E Chung
Keyword(s):  
Basement Membrane ◽  
Rat Kidney ◽  
Ultrastructural Localization ◽  
Duodenal Mucosa ◽  
Basement Membranes ◽  
Rat Tissues ◽  
Mesangial Matrix ◽  
Renal Tubular ◽  
Membrane Components ◽  
Basement Membrane Components

The localization of two noncollagenous components of basement membranes, laminin and entactin, was determined in rat kidney, muscle, and small intestine using electron immunohistochemistry. In the renal glomerulus anti-laminin antibodies reacted with the basement membrane of peripheral capillary loops and with mesangial matrix. In the peripheral capillary loop laminin was preferentially distributed in both laminae rarae. This was in contrast to anti-entactin that localized in peripheral capillary loops but not in mesangial matrix. Even in the peripheral capillary loops it had a different distribution than laminin. Entactin was found predominantly in the lamina rara interna. In renal tubular basement membranes both antibodies localized throughout the full thickness of the basement membranes, with laminin having a preferential distribution in the lamina rara, whereas entactin was more evenly distributed. In the basement membrane of the duodenal mucosa entactin localized in the lamina densa, whereas laminin was present in both laminae. In skeletal muscle both antibodies had similar localization in all basement membranes. These results demonstrate that entactin is an intrinsic component of basement membranes. They also demonstrate that basement membranes from different tissues have subtle variations in content and/or assembly of the different components. It is likely that these variations may be reflected in different functional properties.

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