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; Pediatrics, University of Southern California, Los Angeles, California
Soyoung Park
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; Pediatrics, University of Southern California, Los Angeles, California
Julien Maillard
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; Pediatrics, University of Southern California, Los Angeles, California; Jean-Pierre Aubert Research Center, Inserm U1172, Lille 2 University of Health and Law, Lille, France
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; Pediatrics, University of Southern California, Los Angeles, California; Jean-Pierre Aubert Research Center, Inserm U1172, Lille 2 University of Health and Law, Lille, France
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.
