title: Expression and functional studies of the GDNF family receptor alpha 3 in the pancreas.
abstract: The generation of therapeutic β-cells from human pluripotent stem cells relies on the identification of growth factors that faithfully mimic pancreatic β-cell development in vitro. In this context, the aim of the study was to determine the expression and function of the glial cell line derived neurotrophic factor receptor alpha 3 (GFRα3) and its ligand artemin (Artn) in islet cell development and function. GFRα3 and Artn expression were characterized by in situ hybridization, immunochemistry, and qRT-PCR. We used GFRα3-deficient mice to study GFRα3 function and generated transgenic mice overexpressing Artn in the embryonic pancreas to study Artn function. We found that GFRα3 is expressed at the surface of a subset of Ngn3-positive endocrine progenitors as well as of embryonic α- and β-cells, while Artn is found in the pancreatic mesenchyme. Adult β-cells lack GFRα3 but α-cells express the receptor. GFRα3 was also found in parasympathetic and sympathetic intra-islet neurons as well as in glial cells in the embryonic and adult pancreas. The loss of GFRα3 or overexpression of Artn has no impact on Ngn3 and islet cell formation and maintenance in the embryo. Islet organization and innervation as well as glucose homeostasis is normal in GFRα3-deficient mice suggesting functional redundancy.
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)Institut National de la Santé et de la Recherche Médicale (INSERM) U964, Centre National de Recherche Scientifique (CNRS) UMR 7104, Université de Strasbourg (UdS), 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Nivlet
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)Institut National de la Santé et de la Recherche Médicale (INSERM) U964, Centre National de Recherche Scientifique (CNRS) UMR 7104, Université de Strasbourg (UdS), 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Joel
authors.initials: J
authors.lastname: Herrmann
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)Institut National de la Santé et de la Recherche Médicale (INSERM) U964, Centre National de Recherche Scientifique (CNRS) UMR 7104, Université de Strasbourg (UdS), 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Delia Esteban
authors.initials: DE
authors.lastname: Martin
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)Institut National de la Santé et de la Recherche Médicale (INSERM) U964, Centre National de Recherche Scientifique (CNRS) UMR 7104, Université de Strasbourg (UdS), 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Meunier
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)Institut National de la Santé et de la Recherche Médicale (INSERM) U964, Centre National de Recherche Scientifique (CNRS) UMR 7104, Université de Strasbourg (UdS), 1 Rue Laurent Fries, 67404 Illkirch, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Orvain
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC)Institut National de la Santé et de la Recherche Médicale (INSERM) U964, Centre National de Recherche Scientifique (CNRS) UMR 7104, Université de Strasbourg (UdS), 1 Rue Laurent Fries, 67404 Illkirch, France gradwohl@igbmc.fr.
authors.forename: Gérard
authors.initials: G
authors.lastname: Gradwohl
mesh_terms: D000818:Animals; D015870:Gene Expression; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007515:Islets of Langerhans / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010179:Pancreas / Q000166:cytology / Q000254:growth & development / Q000378:metabolism
chemical_list: C116599:Artn protein, mouse; C494994:Gfra3 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D009419:Nerve Tissue Proteins; D005947:Glucose
keywords: GDNF family receptor alpha 3; artemin; endocrine progenitor; islets of Langerhans; neurogenin3; pancreas; parasympathetic neurons; sympathetic neurons; β-cells