title: Pax4 acts as a key player in pancreas development and plasticity.
abstract: The embryonic development of the pancreas is orchestrated by a complex and coordinated transcription factor network. Neurogenin3 (Neurog3) initiates the endocrine program by activating the expression of additional transcription factors driving survival, proliferation, maturation and lineage allocation of endocrine precursors. Among the direct targets of Neurog3, Pax4 appears as one of the key regulators of β-cell specification. Indeed, mice lacking Pax4 die a few days postpartum, as they develop severe hyperglycemia due to the absence of mature pancreatic β-cells. Pax4 also directly regulates the expression of Arx, a gene that plays a crucial role in α-cell specification. Comparative analysis of Pax4 and Arx mutants, as well as Arx/Pax4 double mutants, showed that islet subtype destiny is mainly directed by cross-repression of the Pax4 and Arx factors. Importantly, the ectopic expression of Pax4 in α-cells was found sufficient to induce their neogenesis and conversion into β-like cells, not only during development but also in adult rodents. Therefore, differentiated endocrine α-cells can be considered as a putative source for insulin-producing β-like cells. These findings have clearly widened our understanding regarding pancreatic development, but they also open new research avenues in the context of diabetes research.
authors: Inserm U1091, CNRS U7277, IBV, Diabetes Genetics Team, FR-06108 Nice, France; Université de Nice-Sophia Antipolis, Laboratoire de Génétique du Développement Normal et Pathologique, FR-06108 Nice, France.
authors: Tiziana
authors: T
authors: Napolitano
authors: Inserm U1091, CNRS U7277, IBV, Diabetes Genetics Team, FR-06108 Nice, France; Université de Nice-Sophia Antipolis, Laboratoire de Génétique du Développement Normal et Pathologique, FR-06108 Nice, France.
authors: Fabio
authors: F
authors: Avolio
authors: Inserm U1091, CNRS U7277, IBV, Diabetes Genetics Team, FR-06108 Nice, France; Université de Nice-Sophia Antipolis, Laboratoire de Génétique du Développement Normal et Pathologique, FR-06108 Nice, France.
authors: Monica
authors: M
authors: Courtney
authors: Inserm U1091, CNRS U7277, IBV, Diabetes Genetics Team, FR-06108 Nice, France; Université de Nice-Sophia Antipolis, Laboratoire de Génétique du Développement Normal et Pathologique, FR-06108 Nice, France.
authors: Andhira
authors: A
authors: Vieira
authors: Inserm U1091, CNRS U7277, IBV, Diabetes Genetics Team, FR-06108 Nice, France; Université de Nice-Sophia Antipolis, Laboratoire de Génétique du Développement Normal et Pathologique, FR-06108 Nice, France.
authors: Noémie
authors: N
authors: Druelle
authors: Inserm U1091, CNRS U7277, IBV, Diabetes Genetics Team, FR-06108 Nice, France; Université de Nice-Sophia Antipolis, Laboratoire de Génétique du Développement Normal et Pathologique, FR-06108 Nice, France.
authors: Nouha
authors: N
authors: Ben-Othman
authors: Inserm U1091, CNRS U7277, IBV, Diabetes Genetics Team, FR-06108 Nice, France; Université de Nice-Sophia Antipolis, Laboratoire de Génétique du Développement Normal et Pathologique, FR-06108 Nice, France.
authors: Biljana
authors: B
authors: Hadzic
authors: Inserm U1091, CNRS U7277, IBV, Diabetes Genetics Team, FR-06108 Nice, France; Université de Nice-Sophia Antipolis, Laboratoire de Génétique du Développement Normal et Pathologique, FR-06108 Nice, France.
authors: Sergi
authors: S
authors: Navarro
authors: Inserm U1091, CNRS U7277, IBV, Diabetes Genetics Team, FR-06108 Nice, France; Université de Nice-Sophia Antipolis, Laboratoire de Génétique du Développement Normal et Pathologique, FR-06108 Nice, France. Electronic address: collombat@unice.fr.
authors: Patrick
authors: P
authors: Collombat
mesh_terms: D000818:Animals; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D051379:Mice; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010179:Pancreas / Q000196:embryology / Q000378:metabolism / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; C491709:PAX4 protein, human; D051761:Paired Box Transcription Factors; C110218:Pax4 protein, mouse
keywords: Arx; Diabetes; Fate specification; Mouse; Pancreatic development; Pax4