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

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 progenitors remain unknown. Here, we show that the loss of the microRNA (miRNA)-processing enzyme in POMC neurons causes metabolic defects, an age-dependent decline in the number of mRNA-expressing cells, and an increased proportion of progenitors acquiring a NPY phenotype. miRNome microarray screening further identified miR-103/107 as candidates that may be involved in the maturation of progenitors. In vitro inhibition of miR-103/107 causes a reduction in the number of -expressing cells and increases the proportion of 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 progenitors and glucose homeostasis.