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

Arregi, Igor LU ; Climent, Maria LU ; Iliev, Dobromir LU ; Strasser, Jürgen; Gouignard, Nadège LU ; Johansson, Jenny K. LU ; Singh, Tania LU ; Mazur, Magdalena LU ; Semb, Henrik LU and Artner, Isabella LU , et al. (2016) In Endocrinology 157(12). p.4615-4631
Abstract

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,... (More)

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.

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published
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Endocrinology
volume
157
issue
12
pages
17 pages
publisher
Endocrine Society
external identifiers
  • scopus:85002279695
  • wos:000392840400016
ISSN
0013-7227
DOI
10.1210/en.2016-1745
language
English
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yes
id
06c6905c-556a-4f8d-884e-ec7836cfc436
date added to LUP
2016-12-29 11:53:13
date last changed
2017-09-18 11:34:07
@article{06c6905c-556a-4f8d-884e-ec7836cfc436,
  abstract     = {<p>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.</p>},
  author       = {Arregi, Igor and Climent, Maria and Iliev, Dobromir and Strasser, Jürgen and Gouignard, Nadège and Johansson, Jenny K. and Singh, Tania and Mazur, Magdalena and Semb, Henrik and Artner, Isabella and Minichiello, Liliana and Pera, Edgar M.},
  issn         = {0013-7227},
  language     = {eng},
  month        = {12},
  number       = {12},
  pages        = {4615--4631},
  publisher    = {Endocrine Society},
  series       = {Endocrinology},
  title        = {Retinol dehydrogenase-10 regulates pancreas organogenesis and endocrine cell differentiation via paracrine retinoic acid signaling},
  url          = {http://dx.doi.org/10.1210/en.2016-1745},
  volume       = {157},
  year         = {2016},
}