Central Dicer-miR-103/107 controls developmental switch of POMC progenitors into NPY neurons and impacts glucose homeostasis

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Abstract

Proopiomelanocortin (POMC) neurons are major negative regulators of energy balance. A distinct developmental property of POMC neurons is that they can adopt an orexigenic neuropeptide Y (NPY) phenotype. However, the mechanisms underlying the differentiation of Pomc progenitors remain unknown. Here, we show that the loss of the microRNA (miRNA)-processing enzyme Dicer in POMC neurons causes metabolic defects, an age-dependent decline in the number of Pomc mRNA-expressing cells, and an increased proportion of Pomc progenitors acquiring a NPY phenotype. miRNome microarray screening further identified miR-103/107 as candidates that may be involved in the maturation of Pomc progenitors. In vitro inhibition of miR-103/107 causes a reduction in the number of Pomc-expressing cells and increases the proportion of Pomc progenitors differentiating into NPY neurons. Moreover, in utero silencing of miR-103/107 causes perturbations in glucose homeostasis. Together, these data suggest a role for prenatal miR-103/107 in the maturation of Pomc progenitors and glucose homeostasis.

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All data generated or analysed during this study are included in the manuscript and supporting files.

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Sophie Croizier

University of Southern California, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-0076-1008
Soyoung Park

University of Southern California, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Julien Maillard

University of Southern California, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Sebastien G Bouret

University of Southern California, Los Angeles, United States

For correspondence
sbouret@chla.usc.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4174-9769

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (DK84142)

Sebastien G Bouret

National Institute of Diabetes and Digestive and Kidney Diseases (DK102780)

Sebastien G Bouret

National Institute of Diabetes and Digestive and Kidney Diseases (DK118401)

Sebastien G Bouret

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: CHLA IACUC protocol #303-16

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.