Elife.: co-auth.: S.Croizier

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

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

Croizier S1,2Park S1,2Maillard J1,2,3Bouret SG1,2,3.


Proopiomelanocortin (POMCneurons are major negative regulators of energy balance. A distinct developmental property of POMC neuronsis that they can adopt an orexigenic neuropeptide Y (NPY) phenotype. However, the mechanisms underlying the differentiation of Pomcprogenitors 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 Pomcprogenitors 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 progenitorsand glucose homeostasis.


Proopiomelanocortin; development; glucose homeostasis; hypothalamus; miRNA; mouse; neuroscience; obesity

PMID: 30311908