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

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

Author information

1
The Saban Research Institute, Developmental Neuroscience Program, Diabetes and Obesity Program, Center for Endocrinology, Diabetes and Metabolism, Children's Hospital Los Angeles, Los Angeles, United States.
2
Pediatrics, University of Southern California, Los Angeles, California.
3
Jean-Pierre Aubert Research Center, Inserm U1172, Lille 2 University of Health and Law, Lille, France.

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

PMID:
30311908
PMCID:
PMC6203430
DOI:
10.7554/eLife.40429
[Indexed for MEDLINE]
Free PMC Article

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