title: Endocrine Pancreas Development and Regeneration: Noncanonical Ideas From Neural Stem Cell Biology.
abstract: Loss of insulin-producing pancreatic islet β-cells is a hallmark of type 1 diabetes. Several experimental paradigms demonstrate that these cells can, in principle, be regenerated from multiple endogenous sources using signaling pathways that are also used during pancreas development. A thorough understanding of these pathways will provide improved opportunities for therapeutic intervention. It is now appreciated that signaling pathways should not be seen as "on" or "off" but that the degree of activity may result in wildly different cellular outcomes. In addition to the degree of operation of a signaling pathway, noncanonical branches also play important roles. Thus, a pathway, once considered as "off" or "low" may actually be highly operational but may be using noncanonical branches. Such branches are only now revealing themselves as new tools to assay them are being generated. A formidable source of noncanonical signal transduction concepts is neural stem cells because these cells appear to have acquired unusual signaling interpretations to allow them to maintain their unique dual properties (self-renewal and multipotency). We discuss how such findings from the neural field can provide a blueprint for the identification of new molecular mechanisms regulating pancreatic biology, with a focus on Notch, Hes/Hey, and hedgehog pathways.
authors.affiliation: Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Masjkur
authors.affiliation: Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany.
authors.forename: Steven W
authors.initials: SW
authors.lastname: Poser
authors.affiliation: Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany.
authors.forename: Polyxeni
authors.initials: P
authors.lastname: Nikolakopoulou
authors.affiliation: First Department of Pediatrics, University of Athens Medical School and Aghia Sophia Children's Hospital, Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Chrousos
authors.affiliation: Lieber Institute for Brain Development, Baltimore, MD.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: McKay
authors.affiliation: Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany.
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.affiliation: Diabetes Research Group, Division of Diabetes & Nutritional Sciences, King's College London, London, U.K.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Jones
authors.affiliation: Department of Internal Medicine III, Technische Universität Dresden, Dresden, Germany Center for Regenerative Therapies Dresden, Dresden, Germany Department of Stem Cell Biology, Centre for Biomolecular Sciences, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, U.K. andreas.theotokis@uniklinikum-dresden.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Androutsellis-Theotokis
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D053823:Hedgehog Proteins / Q000502:physiology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D058953:Neural Stem Cells / Q000502:physiology*; D038081:Organogenesis / Q000502:physiology; D010179:Pancreas / Q000196:embryology / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D053823:Hedgehog Proteins