title: Loss of Pancreas upon Activated Wnt Signaling Is Concomitant with Emergence of Gastrointestinal Identity.
abstract: Organ formation is achieved through the complex interplay between signaling pathways and transcriptional cascades. The canonical Wnt signaling pathway plays multiple roles during embryonic development including patterning, proliferation and differentiation in distinct tissues. Previous studies have established the importance of this pathway at multiple stages of pancreas formation as well as in postnatal organ function and homeostasis. In mice, gain-of-function experiments have demonstrated that activation of the canonical Wnt pathway results in pancreatic hypoplasia, a phenomenon whose underlying mechanisms remains to be elucidated. Here, we show that ectopic activation of epithelial canonical Wnt signaling causes aberrant induction of gastric and intestinal markers both in the pancreatic epithelium and mesenchyme, leading to the development of gut-like features. Furthermore, we provide evidence that β -catenin-induced impairment of pancreas formation depends on Hedgehog signaling. Together, our data emphasize the developmental plasticity of pancreatic progenitors and further underscore the key role of precise regulation of signaling pathways to maintain appropriate organ boundaries.
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla, Spain.|Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Muñoz-Bravo
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla, Spain.|Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Flores-Martínez
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla, Spain.|Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain.
authors.forename: Griselda
authors.initials: G
authors.lastname: Herrero-Martin
authors.affiliation: Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, United States of America.
authors.forename: Sapna
authors.initials: S
authors.lastname: Puri
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Makoto Mark
authors.initials: MM
authors.lastname: Taketo
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Sevilla, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Madrid, Spain.
authors.forename: Anabel
authors.initials: A
authors.lastname: Rojas
authors.affiliation: Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, United States of America.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hebrok
authors.affiliation: Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Universitario Virgen del Rocío, Sevilla, Spain.|Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Consejo Superior de Investigaciones Científicas/Universidad de Sevilla, Sevilla, Spain.
authors.forename: David A
authors.initials: DA
authors.lastname: Cano
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism / Q000601:surgery; D004848:Epithelium / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: C495267:CTNNB1 protein, mouse; D053823:Hedgehog Proteins; D018398:Homeodomain Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051176:beta Catenin; C084010:pancreatic and duodenal homeobox 1 protein