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

Sophie Croizier , Soyoung Park , Julien Maillard , Sébastien G. Bouret (1)

1 JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837

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.

Mots clés: Proopiomelanocortin, development, glucose homeostasis, hypothalamus, miRNA, mouse, neuroscience, obesity

Domaines: Sciences du Vivant [q-bio]

Sophie Croizier, Soyoung Park, Julien Maillard, Sébastien G. Bouret. Central Dicer-miR-103/107 controls developmental switch of POMC progenitors into NPY neurons and impacts glucose homeostasis. eLife, 2018, 7, ⟨10.7554/eLife.40429⟩. ⟨hal-02375382⟩