title: Competence of failed endocrine progenitors to give rise to acinar but not ductal cells is restricted to early pancreas development.
abstract: During mouse pancreas development, the transient expression of Neurogenin3 (Neurog3) in uncommitted pancreas progenitors is required to determine endocrine destiny. However it has been reported that Neurog3-expressing cells can eventually adopt acinar or ductal fates and that Neurog3 levels were important to secure the islet destiny. It is not known whether the competence of Neurog3-induced cells to give rise to non-endocrine lineages is an intrinsic property of these progenitors or depends on pancreas developmental stage. Using temporal genetic labeling approaches we examined the dynamic of endocrine progenitor differentiation and explored the plasticity of Neurog3-induced cells throughout development. We found that Neurog3(+) progenitors develop into hormone-expressing cells in a fast process taking less then 10h. Furthermore, fate-mapping studies in heterozygote (Neurog3(CreERT/+)) and Neurog3-deficient (Neurog3(CreERT/CreERT)) embryos revealed that Neurog3-induced cells have different potential over time. At the early bud stage, failed endocrine progenitors can adopt acinar or ductal fate, whereas later in the branching pancreas they do not contribute to the acinar lineage but Neurog3-deficient cells eventually differentiate into duct cells. Thus these results provide evidence that the plasticity of Neurog3-induced cells becomes restricted during development. Furthermore these data suggest that during the secondary transition, endocrine progenitor cells arise from bipotent precursors already committed to the duct/endocrine lineages and not from domain of cells having distinct potentialities.
authors: Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale U964, Centre National de Recherche Scientifique UMR 7104, Université de Strasbourg, 67404 Illkirch, France.
authors: Anthony
authors: A
authors: Beucher
authors: Mercè
authors: M
authors: Martín
authors: Caroline
authors: C
authors: Spenle
authors: Martine
authors: M
authors: Poulet
authors: Caitlin
authors: C
authors: Collin
authors: Gérard
authors: G
authors: Gradwohl
mesh_terms: D061354:Acinar Cells / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency / Q000378:metabolism; D019521:Body Patterning; D002454:Cell Differentiation; D019070:Cell Lineage; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D004703:Endocrine System / Q000166:cytology* / Q000196:embryology*; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D006728:Hormones / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism; D010183:Pancreatic Ducts / Q000166:cytology* / Q000196:embryology* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013997:Time Factors; D060726:Torso / Q000196:embryology
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D006728:Hormones; D009419:Nerve Tissue Proteins; C407737:Neurog3 protein, mouse