title: Ectodermal Wnt signaling regulates abdominal myogenesis during ventral body wall development.
abstract: Defects of the ventral body wall are prevalent birth anomalies marked by deficiencies in body wall closure, hypoplasia of the abdominal musculature and multiple malformations across a gamut of organs. However, the mechanisms underlying ventral body wall defects remain elusive. Here, we investigated the role of Wnt signaling in ventral body wall development by inactivating Wls or β-catenin in murine abdominal ectoderm. The loss of Wls in the ventral epithelium, which blocks the secretion of Wnt proteins, resulted in dysgenesis of ventral musculature and genito-urinary tract during embryonic development. Molecular analyses revealed that the dermis and myogenic differentiation in the underlying mesenchymal progenitor cells was perturbed by the loss of ectodermal Wls. The activity of the Wnt-Pitx2 axis was impaired in the ventral mesenchyme of the mutant body wall, which partially accounted for the defects in ventral musculature formation. In contrast, epithelial depletion of β-catenin or Wnt5a did not resemble the body wall defects in the ectodermal Wls mutant. These findings indicate that ectodermal Wnt signaling instructs the underlying mesodermal specification and abdominal musculature formation during ventral body wall development, adding evidence to the theory that ectoderm-mesenchyme signaling is a potential unifying mechanism for the origin of ventral body wall defects.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Hanjun
authors.initials: H
authors.lastname: Li
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Cao
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Yiyun
authors.initials: Y
authors.lastname: Yao
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Cheng
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Rujiang
authors.initials: R
authors.lastname: Zhou
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Zhengju
authors.initials: Z
authors.lastname: Yao
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address: xzguo2005@sjtu.edu.cn.
authors.forename: Xizhi
authors.initials: X
authors.lastname: Guo
mesh_terms: D000005:Abdomen / Q000196:embryology* / Q000254:growth & development; D000818:Animals; D019521:Body Patterning / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D004475:Ectoderm / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D004622:Embryo, Mammalian / Q000196:embryology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008648:Mesoderm / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024510:Muscle Development / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D014566:Urogenital System / Q000196:embryology / Q000254:growth & development; D051153:Wnt Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics*; D000071818:Wnt-5a Protein; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*; D000097577:Homeobox Protein PITX2
chemical_list: D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051176:beta Catenin; D000097577:Homeobox Protein PITX2; C495267:CTNNB1 protein, mouse; C545200:Gpr177 protein, mouse; C084119:MSX2 protein; C438615:Wnt5a protein, mouse
keywords: Abdominal musculature; Ectoderm; Pitx2; Ventral body wall; Wls