title: Constitutive activation of ectodermal β-catenin induces ectopic outgrowths at various positions in mouse embryo and affects abdominal ventral body wall closure.
abstract: Vertebrate limbs originate from the lateral plate mesoderm (LPM) and the overlying ectoderm. While normal limb formation in defined regions has been well studied, the question of whether other positions retain limb-forming potential has not been fully investigated in mice. By ectopically activating β-catenin in the ectoderm with Msx2-cre, we observed that local tissue outgrowths were induced, which either progressed into limb-like structure within the inter-limb flank or formed extra tissues in other parts of the mouse embryo. In the presumptive abdominal region of severely affected embryos, ectopic limb formation was coupled with impaired abdominal ventral body wall (AVBW) closure, which indicates the existence of a potential counterbalance of limb formation and AVBW closure. At the molecular level, constitutive β-catenin activation was sufficient to trigger, but insufficient to maintain the ectopic expression of a putative limb-inducing factor, Fgf8, in the ectoderm. These findings provide new insight into the mechanism of limb formation and AVBW closure, and the crosstalk between the Wnt/β-catenin pathway and Fgf signal.
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Sixia
authors.initials: S
authors.lastname: Huang
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Luwan Branch, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Dermatology, Luwan Branch, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Yingwei
authors.initials: Y
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, PR China.
authors.forename: Yixin
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Yushu
authors.initials: Y
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, PR China; Department of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Shigang
authors.initials: S
authors.lastname: He
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China; Regenerative Medicine Institute, School of Medicine, National University of Ireland Galway, Newcastle Road, Galway, Ireland.
authors.forename: Sanbing
authors.initials: S
authors.lastname: Shen
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Ji
authors.initials: J
authors.lastname: Wu
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Baojie
authors.initials: B
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, PR China.
authors.forename: Xizhi
authors.initials: X
authors.lastname: Guo
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: He
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
mesh_terms: D034861:Abdominal Wall / Q000196:embryology*; D000818:Animals; D019521:Body Patterning; D004475:Ectoderm / Q000196:embryology* / Q000378:metabolism*; D004622:Embryo, Mammalian / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000378:metabolism; D053823:Hedgehog Proteins / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D051957:MSX1 Transcription Factor / Q000378:metabolism; D051379:Mice; D009154:Mutation / Q000235:genetics; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D053823:Hedgehog Proteins; D051957:MSX1 Transcription Factor; C484084:Msx1 protein, mouse; C465570:Shh protein, mouse; D051176:beta Catenin; D051524:Fibroblast Growth Factor 8; C045073:Cre recombinase; D019426:Integrases