Pax4 acts as a key player in pancreas development and plasticity

Seminars in Cell & Developmental Biology
Tiziana NapolitanoPatrick Collombat

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 pancrea...Continue Reading

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Citations

Apr 26, 2016·Canine Genetics and Epidemiology·Christina BreitenbuecherAnita M Oberbauer
Mar 5, 2016·The Journal of Endocrinology·Charlotte BarbieuxDomenico Bosco
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Mar 15, 2018·Journal of Clinical Medicine·Gabriela Da Silva Xavier
Jul 14, 2017·Communicative & Integrative Biology·Tiziana NapolitanoPatrick Collombat
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Jan 21, 2021·International Journal of Molecular Sciences·Giuseppina Emanuela GriecoFrancesco Dotta
Jul 28, 2020·Mechanisms of Development·Sivasangari BalakrishnanChidambaram Prahalathan

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