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Tania Singh

Postdoc

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Retinol dehydrogenase-10 regulates pancreas organogenesis and endocrine cell differentiation via paracrine retinoic acid signaling

Author

  • Igor Arregi
  • Maria Climent
  • Dobromir Iliev
  • Jürgen Strasser
  • Nadège Gouignard
  • Jenny K. Johansson
  • Tania Singh
  • Magdalena Mazur
  • Henrik Semb
  • Isabella Artner
  • Liliana Minichiello
  • Edgar M. Pera

Summary, in English

Vitamin A-derived retinoic acid (RA) signals are critical for the development of several organs, including the pancreas. However, the tissue-specific control of RA synthesis in organ and cell lineage development has only poorly been addressed in vivo. Here, we show that retinol dehydrogenase-10 (Rdh10), a key enzyme in embryonic RA production, has important functions in pancreas organogenesis and endocrine cell differentiation. Rdh10 was expressed in the developing pancreas epithelium and surrounding mesenchyme. Rdh10 null mutant mouse embryos exhibited dorsal pancreas agenesis and a hypoplastic ventral pancreas with retarded tubulogenesis and branching. Conditional disruption of Rdh10 from the endoderm caused increased mortality, reduced body weight, and lowered blood glucose levels after birth. Endodermal Rdh10 deficiency led to a smaller dorsal pancreas with a reduced density of early glucagonβ and insulinβ cells. During the secondary transition, the reduction of Neurogenin3β endocrine progenitors in the mutant dorsal pancreas accounted for fewer β-and α-cells. Changes in the expression of β-and α-cellspecific transcription factors indicated that Rdh10 might also participate in the terminal differentiation of endocrine cells. Together, our results highlight the importance of both mesenchymal andepithelialRdh10forpancreogenesisandthefirstwaveofendocrinecell differentiation.Wefurther propose a model in which the Rdh10-expressing exocrine tissue acts as an essential source ofRAsignals in the second wave of endocrine cell differentiation.

Department/s

  • Stem Cell Center
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • StemTherapy: National Initiative on Stem Cells for Regenerative Therapy

Publishing year

2016-12-01

Language

English

Pages

4615-4631

Publication/Series

Endocrinology

Volume

157

Issue

12

Document type

Journal article

Publisher

Oxford University Press

Topic

  • Cell and Molecular Biology

Status

Published

ISBN/ISSN/Other

  • ISSN: 0013-7227