Matches in SemOpenAlex for { <https://semopenalex.org/work/W1979305468> ?p ?o ?g. }
- W1979305468 endingPage "275" @default.
- W1979305468 startingPage "264" @default.
- W1979305468 abstract "Midline defects account for approximately 5% of congenital abnormalities observed at birth. However, the molecular mechanisms underlying the formation of the ventral body wall are not well understood. Recent studies linked mutations in Porcupine—an O-acetyl transferase mediating Wnt ligand acylation—with defects in the thoracic body wall. We hypothesized that anomalous Wnt signaling is involved in the pathogenesis of defective closure of the thoracic body wall. We generated a mouse model wherein Wntless (Wls), which encodes a cargo receptor mediating secretion of Wnt ligands, was conditionally deleted from the developing mesenchyme using Dermo1Cre mice. Wlsf/f;Dermo1Cre/+ embryos died during mid-gestation. At E13.5, skeletal defects were observed in the forelimbs, jaw, and rib cage. At E14.5, midline defects in the thoracic body wall began to emerge: the sternum failed to fuse and the heart protruded through the body wall at the midline (ectopia cordis). To determine the molecular mechanism underlying the phenotype observed in Wlsf/f;Dermo1Cre/+ embryos, we tested whether Wnt/β-catenin signaling was operative in developing the embryonic ventral body wall using Axin2LacZ and BatGal reporter mice. While Wnt/β-catenin signaling activity was observed at the midline of the ventral body wall before sternal fusion, this pattern of activity was altered and scattered throughout the body wall after mesenchymal deletion of Wls. Mesenchymal cell migration was disrupted in Wlsf/f;Dermo1Cre/+ thoracic body wall partially due to anomalous β-catenin independent Wnt signaling as determined by in vitro assays. Deletion of Lrp5 and Lrp6 receptors, which mediate Wnt/β-catenin signaling in the mesenchyme, partially recapitulated the phenotype observed in the chest midline of Wlsf/f;Dermo1Cre/+ embryos supporting a role for Wnt/β-catenin signaling activity in the normal formation of the ventral body wall mesenchyme. We conclude that Wls-mediated secretion of Wnt ligands from the developing ventral body wall mesenchyme plays a critical role in fusion of the sternum and closure of the secondary body wall. Thus, impaired Wls activity in the ventral body wall mesenchyme is a mechanism underlying ectopia cordis and unfused sternum." @default.
- W1979305468 created "2016-06-24" @default.
- W1979305468 creator A5001813162 @default.
- W1979305468 creator A5017191773 @default.
- W1979305468 creator A5019485398 @default.
- W1979305468 creator A5025386832 @default.
- W1979305468 creator A5035064986 @default.
- W1979305468 creator A5036883465 @default.
- W1979305468 date "2015-05-01" @default.
- W1979305468 modified "2023-10-16" @default.
- W1979305468 title "Mesenchymal Wnt signaling promotes formation of sternum and thoracic body wall" @default.
- W1979305468 cites W1487100917 @default.
- W1979305468 cites W1960895270 @default.
- W1979305468 cites W1967053032 @default.
- W1979305468 cites W1973982607 @default.
- W1979305468 cites W1977462853 @default.
- W1979305468 cites W1980861932 @default.
- W1979305468 cites W1981625810 @default.
- W1979305468 cites W1981888346 @default.
- W1979305468 cites W1982204468 @default.
- W1979305468 cites W1985915030 @default.
- W1979305468 cites W1994816148 @default.
- W1979305468 cites W1995230240 @default.
- W1979305468 cites W2002792135 @default.
- W1979305468 cites W2017400430 @default.
- W1979305468 cites W2021970320 @default.
- W1979305468 cites W2025453970 @default.
- W1979305468 cites W2027284916 @default.
- W1979305468 cites W2030627501 @default.
- W1979305468 cites W2047383747 @default.
- W1979305468 cites W2052723831 @default.
- W1979305468 cites W2054702166 @default.
- W1979305468 cites W2061008214 @default.
- W1979305468 cites W2065824248 @default.
- W1979305468 cites W2069441205 @default.
- W1979305468 cites W2070044720 @default.
- W1979305468 cites W2074149867 @default.
- W1979305468 cites W2074978112 @default.
- W1979305468 cites W2076627274 @default.
- W1979305468 cites W2083308747 @default.
- W1979305468 cites W2095542272 @default.
- W1979305468 cites W2104010513 @default.
- W1979305468 cites W2107558446 @default.
- W1979305468 cites W2112763851 @default.
- W1979305468 cites W2117539897 @default.
- W1979305468 cites W2122109009 @default.
- W1979305468 cites W2139945482 @default.
- W1979305468 cites W2142872318 @default.
- W1979305468 cites W2154041910 @default.
- W1979305468 cites W2155861726 @default.
- W1979305468 cites W2156820761 @default.
- W1979305468 cites W2164884961 @default.
- W1979305468 cites W565127267 @default.
- W1979305468 doi "https://doi.org/10.1016/j.ydbio.2015.02.014" @default.
- W1979305468 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4424168" @default.
- W1979305468 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25727890" @default.
- W1979305468 hasPublicationYear "2015" @default.
- W1979305468 type Work @default.
- W1979305468 sameAs 1979305468 @default.
- W1979305468 citedByCount "24" @default.
- W1979305468 countsByYear W19793054682015 @default.
- W1979305468 countsByYear W19793054682016 @default.
- W1979305468 countsByYear W19793054682017 @default.
- W1979305468 countsByYear W19793054682018 @default.
- W1979305468 countsByYear W19793054682019 @default.
- W1979305468 countsByYear W19793054682020 @default.
- W1979305468 countsByYear W19793054682022 @default.
- W1979305468 countsByYear W19793054682023 @default.
- W1979305468 crossrefType "journal-article" @default.
- W1979305468 hasAuthorship W1979305468A5001813162 @default.
- W1979305468 hasAuthorship W1979305468A5017191773 @default.
- W1979305468 hasAuthorship W1979305468A5019485398 @default.
- W1979305468 hasAuthorship W1979305468A5025386832 @default.
- W1979305468 hasAuthorship W1979305468A5035064986 @default.
- W1979305468 hasAuthorship W1979305468A5036883465 @default.
- W1979305468 hasBestOaLocation W19793054682 @default.
- W1979305468 hasConcept C105702510 @default.
- W1979305468 hasConcept C107300179 @default.
- W1979305468 hasConcept C137620995 @default.
- W1979305468 hasConcept C198826908 @default.
- W1979305468 hasConcept C2776340970 @default.
- W1979305468 hasConcept C2778620301 @default.
- W1979305468 hasConcept C2779131293 @default.
- W1979305468 hasConcept C2779324961 @default.
- W1979305468 hasConcept C62478195 @default.
- W1979305468 hasConcept C86803240 @default.
- W1979305468 hasConcept C95444343 @default.
- W1979305468 hasConceptScore W1979305468C105702510 @default.
- W1979305468 hasConceptScore W1979305468C107300179 @default.
- W1979305468 hasConceptScore W1979305468C137620995 @default.
- W1979305468 hasConceptScore W1979305468C198826908 @default.
- W1979305468 hasConceptScore W1979305468C2776340970 @default.
- W1979305468 hasConceptScore W1979305468C2778620301 @default.
- W1979305468 hasConceptScore W1979305468C2779131293 @default.
- W1979305468 hasConceptScore W1979305468C2779324961 @default.
- W1979305468 hasConceptScore W1979305468C62478195 @default.
- W1979305468 hasConceptScore W1979305468C86803240 @default.
- W1979305468 hasConceptScore W1979305468C95444343 @default.