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

Author:

Croizier Sophie12ORCID,Park Soyoung12,Maillard Julien123,Bouret Sebastien G123ORCID

Affiliation:

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.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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