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

Elife. 2018 Oct 12:7:e40429. doi: 10.7554/eLife.40429.

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 PomcmRNA-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.

Keywords: Proopiomelanocortin; development; glucose homeostasis; hypothalamus; miRNA; mouse; neuroscience; obesity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation*
  • Gene Expression Regulation, Developmental*
  • Glucose / metabolism
  • Homeostasis
  • Mice
  • MicroRNAs / metabolism*
  • Neurons / physiology*
  • Neuropeptide Y / biosynthesis*
  • Pro-Opiomelanocortin / biosynthesis*

Substances

  • MIRN103 microRNA, mouse
  • MIRN107 microRNA, mouse
  • MicroRNAs
  • Neuropeptide Y
  • Pro-Opiomelanocortin
  • Glucose