Mesenchymal Wnt signaling promotes formation of sternum and thoracic body wall

Developmental Biology
John SnowballDebora Sinner

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. Wls(f/f);Dermo1(Cre/+) 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 Wls(f/f);Dermo1(Cre/+) embryos, we tested whether Wnt/β-catenin signaling was operative in developing the embryonic ventral body wall using Axin2(LacZ) and BatGal reporter mice. While Wnt/β-catenin si...Continue Reading

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Citations

Jan 23, 2016·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·Rudolf Happle
Jun 21, 2015·Developmental Biology·John SnowballDebora Sinner
Sep 14, 2016·American Journal of Medical Genetics. Part a·Laura MaryMaria Cristina Antal
Dec 13, 2016·American Journal of Physiology. Lung Cellular and Molecular Physiology·Jennifer M S SucreBrigitte N Gomperts
Jun 20, 2018·Birth Defects Research·John M DeSesso, Anthony R Scialli
Aug 2, 2018·Frontiers in Pediatrics·Claudiu MărgineanManuela Cucerea
Jun 20, 2019·American Journal of Respiratory and Critical Care Medicine·Debora I SinnerBruce C Trapnell
Dec 15, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Gabriel L GaleaPhilippa Francis-West

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