Central Dicer-miR-103/107 controls developmental switch of POMC progenitors into NPY neurons and impacts glucose homeostasis
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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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
Copyright
© 2018, Croizier et al.
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.
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