Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans.
In mammals, Bone Morphogenetic Protein (BMP) pathway signaling is important for the growth and homeostasis of extracellular matrix, including basement membrane remodeling, scarring, and bone growth. A conserved BMP member in Caenorhabditis elegans, DBL-1, regulates body length in a dose-sensitive ma...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4094471?pdf=render |
| _version_ | 1818286731929059328 |
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| author | Robbie D Schultz Emily E Bennett E Ann Ellis Tina L Gumienny |
| author_facet | Robbie D Schultz Emily E Bennett E Ann Ellis Tina L Gumienny |
| author_sort | Robbie D Schultz |
| collection | DOAJ |
| description | In mammals, Bone Morphogenetic Protein (BMP) pathway signaling is important for the growth and homeostasis of extracellular matrix, including basement membrane remodeling, scarring, and bone growth. A conserved BMP member in Caenorhabditis elegans, DBL-1, regulates body length in a dose-sensitive manner. Loss of DBL-1 pathway signaling also results in increased anesthetic sensitivity. However, the physiological basis of these pleiotropic phenotypes is largely unknown. We created a DBL-1 over-expressing strain and show that sensitivity to anesthetics is inversely related to the dose of DBL-1. Using pharmacological, genetic analyses, and a novel dye permeability assay for live, microwave-treated animals, we confirm that DBL-1 is required for the barrier function of the cuticle, a specialized extracellular matrix. We show that DBL-1 signaling is required to prevent animals from forming tail-entangled aggregates in liquid. Stripping lipids off the surface of wild-type animals recapitulates this phenotype. Finally, we find that DBL-1 signaling affects ultrastructure of the nematode cuticle in a dose-dependent manner, as surface lipid content and cuticular organization are disrupted in animals with genetically altered DBL-1 levels. We propose that the lipid layer coating the nematode cuticle normally prevents tail entanglement, and that reduction of this layer by loss of DBL-1 signaling promotes aggregation. This work provides a physiological mechanism that unites the DBL-1 signaling pathway roles of not only body size regulation and drug responsiveness, but also the novel Hoechst 33342 staining and aggregation phenotypes, through barrier function, content, and organization of the cuticle. |
| first_indexed | 2024-12-13T01:29:16Z |
| format | Article |
| id | doaj.art-416b4957938248e189c192ff6a5c15b0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T01:29:16Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-416b4957938248e189c192ff6a5c15b02022-12-22T00:04:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10192910.1371/journal.pone.0101929Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans.Robbie D SchultzEmily E BennettE Ann EllisTina L GumiennyIn mammals, Bone Morphogenetic Protein (BMP) pathway signaling is important for the growth and homeostasis of extracellular matrix, including basement membrane remodeling, scarring, and bone growth. A conserved BMP member in Caenorhabditis elegans, DBL-1, regulates body length in a dose-sensitive manner. Loss of DBL-1 pathway signaling also results in increased anesthetic sensitivity. However, the physiological basis of these pleiotropic phenotypes is largely unknown. We created a DBL-1 over-expressing strain and show that sensitivity to anesthetics is inversely related to the dose of DBL-1. Using pharmacological, genetic analyses, and a novel dye permeability assay for live, microwave-treated animals, we confirm that DBL-1 is required for the barrier function of the cuticle, a specialized extracellular matrix. We show that DBL-1 signaling is required to prevent animals from forming tail-entangled aggregates in liquid. Stripping lipids off the surface of wild-type animals recapitulates this phenotype. Finally, we find that DBL-1 signaling affects ultrastructure of the nematode cuticle in a dose-dependent manner, as surface lipid content and cuticular organization are disrupted in animals with genetically altered DBL-1 levels. We propose that the lipid layer coating the nematode cuticle normally prevents tail entanglement, and that reduction of this layer by loss of DBL-1 signaling promotes aggregation. This work provides a physiological mechanism that unites the DBL-1 signaling pathway roles of not only body size regulation and drug responsiveness, but also the novel Hoechst 33342 staining and aggregation phenotypes, through barrier function, content, and organization of the cuticle.http://europepmc.org/articles/PMC4094471?pdf=render |
| spellingShingle | Robbie D Schultz Emily E Bennett E Ann Ellis Tina L Gumienny Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans. PLoS ONE |
| title | Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans. |
| title_full | Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans. |
| title_fullStr | Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans. |
| title_full_unstemmed | Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans. |
| title_short | Regulation of extracellular matrix organization by BMP signaling in Caenorhabditis elegans. |
| title_sort | regulation of extracellular matrix organization by bmp signaling in caenorhabditis elegans |
| url | http://europepmc.org/articles/PMC4094471?pdf=render |
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