Central <i>Dicer</i>-miR-103/107 Controls Developmental Switch of POMC Progenitors into NPY Neurons and Impacts Glucose Homeostasis

Croizier, Sophie; Maillard, Julien; Bouret, Sébastien G.

doi:10.1101/381921

Cited by 2 publications

(4 citation statements)

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“…The loss of Efnb1 in POMC neurons is associated with alterations in glucose tolerance and losses of parasympathetic nerve activity and insulin secretion. These findings are consistent with previous studies, which reported that affecting either POMC signaling, circuits or POMC neuron survival leads to impaired glucose homeostasis (10–12). Surprisingly, loss of Efnb1 in POMC neurons does not perturb food intake or body weight.…”

Section: Discussionsupporting

confidence: 94%

“…P6, P14, and P22 Pomc -Cre;tdTomato male mice (n=2-3 animals/age), 16-18 week-old Pomc -Cre;tdTomato; Efnb1 loxP/0 , Pomc -Cre;tdTomato, Pomc -Cre;tdTomato; Efnb2 loxP/loxP , and Pomc -Cre;tdTomato; Efnb1 loxP/loxP , Pomc -Cre;tdTomato; Efnb2 loxP/loxP , Pomc -Cre;tdTomato female mice were transcardially perfused with 4% PFA (n=3/group). 20 µm-thick brain and pancreas sections were processed for immunofluorescence using standard procedures (10,52,58). The primary antibodies used for IHC were as follows: rabbit anti-vGLUT2 (1:500, Synaptic Systems), rabbit anti-VAChT (1:500, Synaptic Systems), guinea-pig anti-insulin (1:500, Abcam).…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, alterations in POMC signaling, circuits, or neuronal survival are associated with disruption of glucose homeostasis. (10–12).…”

Section: Introductionmentioning

confidence: 99%

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EphrinB1 modulates glutamatergic inputs into POMC neurons and controls glucose homeostasis

Gervais

Picard

Thorens

et al. 2020

Preprint

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Proopiomelanocortin (POMC) neurons are major regulators of energy balance and glucose homeostasis. In addition to being regulated by hormones and nutrients, POMC neurons are controlled by glutamatergic input originating from multiple brain regions. However, the factors involved in the formation of glutamatergic inputs and how they contribute to bodily functions remain largely unknown. Here, we show that during the development of glutamatergic inputs, POMC neurons exhibit enriched expression of the Efnb1 (EphrinB1) and Efnb2 (EphrinB2) genes, which are known to control excitatory synapse formation. In vitro silencing and in vivo loss of Efnb1 or Efnb2 in POMC neurons decreases the amount of glutamatergic inputs into these neurons. We found that mice lacking Efnb1 in POMC neurons display impaired glucose tolerance due to blunted vagus nerve activity and decreased insulin secretion. However, mice lacking Efnb2 in POMC neurons showed no deregulation of insulin secretion and only mild alterations in feeding behavior and gluconeogenesis. Collectively, our data demonstrate the role of ephrins in controlling excitatory input amount into POMC neurons and show an isotype-specific role of ephrins on the regulation of glucose homeostasis and feeding.

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Section: Discussionsupporting

confidence: 94%

Section: Methodsmentioning

confidence: 99%

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EphrinB1 modulates glutamatergic inputs into POMC neurons and controls glucose homeostasis

Gervais

Picard

Thorens

et al. 2020

Preprint

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“…The ARH contains neuronal populations that are topographically distributed (Croizier et al, 2010). Of which, POMC‐expressing neurons were mainly observed in the dorsolateral ARH while NPY/AgRP‐coexpressing neurons mostly localized in the ventromedial ARH close to the medial eminence and the third ventricle (Figure 15a,f,g) (Croizier et al, 2018; Lein et al, 2007). By using immunohistochemical approaches, confocal imaging and 3D reconstruction, we observed PHAL‐positive putative terminal boutons surrounding and in contact with POMC‐expressing neurons (Figure 15a–d).…”

Section: Resultsmentioning

confidence: 99%

Projections from the dorsomedial division of the bed nucleus of the stria terminalis to hypothalamic nuclei in the mouse

Barbier

González

Houdayer

et al. 2020

J of Comparative Neurology

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As stressful environment is a potent modulator of feeding, we seek in the present work to decipher the neuroanatomical basis for an interplay between stress and feeding behaviors. For this, we combined anterograde and retrograde tracing with immunohistochemical approaches to investigate the patterns of projections between the dorsomedial division of the bed nucleus of the stria terminalis (BNST), well connected to the amygdala, and hypothalamic structures such as the paraventricular (PVH) and dorsomedial (DMH), the arcuate (ARH) nuclei and the lateral hypothalamic areas (LHA) known to control feeding and motivated behaviors. We particularly focused our study on afferences to proopiomelanocortin (POMC), agouti‐related peptide (AgRP), melanin‐concentrating‐hormone (MCH) and orexin (ORX) neurons characteristics of the ARH and the LHA, respectively. We found light to intense innervation of all these hypothalamic nuclei. We particularly showed an innervation of POMC, AgRP, MCH and ORX neurons by the dorsomedial and dorsolateral divisions of the BNST. Therefore, these results lay the foundation for a better understanding of the neuroanatomical basis of the stress‐related feeding behaviors.

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Central Dicer-miR-103/107 Controls Developmental Switch of POMC Progenitors into NPY Neurons and Impacts Glucose Homeostasis

Abstract: 33Proopiomelanocortin ( 43Moreover, in utero silencing of miR-103/107 causes perturbations in glucose homeostasis.

Cited by 2 publications

References 45 publications

EphrinB1 modulates glutamatergic inputs into POMC neurons and controls glucose homeostasis

EphrinB1 modulates glutamatergic inputs into POMC neurons and controls glucose homeostasis

Projections from the dorsomedial division of the bed nucleus of the stria terminalis to hypothalamic nuclei in the mouse

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