» Articles » PMID: 30311908

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

Overview
Journal Elife
Specialty Biology
Date 2018 Oct 13
PMID 30311908
Citations 21
Authors
Affiliations
Soon will be listed here.
Abstract

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.

Citing Articles

Control of tuberal hypothalamic development and its implications in metabolic disorders.

Placzek M, Chinnaiya K, Kim D, Blackshaw S Nat Rev Endocrinol. 2024; 21(2):118-130.

PMID: 39313573 PMC: 11864813. DOI: 10.1038/s41574-024-01036-1.


Single cell tracing of Pomc neurons reveals recruitment of 'Ghost' subtypes with atypical identity in a mouse model of obesity.

Leon S, Simon V, Lee T, Steuernagel L, Clark S, Biglari N Nat Commun. 2024; 15(1):3443.

PMID: 38658557 PMC: 11043070. DOI: 10.1038/s41467-024-47877-2.


Casein kinase 1α is required to maintain murine hypothalamic pro-opiomelanocortin expression.

Lu C, Zhang J, Wang B, Gao Q, Ma K, Pei S iScience. 2023; 26(5):106670.

PMID: 37168577 PMC: 10165255. DOI: 10.1016/j.isci.2023.106670.


Mechanisms mediating the impact of maternal obesity on offspring hypothalamic development and later function.

Furigo I, Dearden L Front Endocrinol (Lausanne). 2023; 13:1078955.

PMID: 36619540 PMC: 9813846. DOI: 10.3389/fendo.2022.1078955.


Neuroendocrine microRNAs linked to energy homeostasis: future therapeutic potential.

Mak K, Mustafa A, Belsham D Pharmacol Rep. 2022; 74(5):774-789.

PMID: 36083576 DOI: 10.1007/s43440-022-00409-5.


References
1.
Coupe B, Bouret S . Development of the hypothalamic melanocortin system. Front Endocrinol (Lausanne). 2013; 4:38. PMC: 3608914. DOI: 10.3389/fendo.2013.00038. View

2.
Gautron L, Elmquist J, Williams K . Neural control of energy balance: translating circuits to therapies. Cell. 2015; 161(1):133-145. PMC: 4392840. DOI: 10.1016/j.cell.2015.02.023. View

3.
Zehir A, Hua L, Maska E, Morikawa Y, Cserjesi P . Dicer is required for survival of differentiating neural crest cells. Dev Biol. 2010; 340(2):459-67. PMC: 2878775. DOI: 10.1016/j.ydbio.2010.01.039. View

4.
Balthasar N, Coppari R, McMinn J, Liu S, Lee C, Tang V . Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron. 2004; 42(6):983-91. DOI: 10.1016/j.neuron.2004.06.004. View

5.
Damiani D, Alexander J, ORourke J, McManus M, Jadhav A, Cepko C . Dicer inactivation leads to progressive functional and structural degeneration of the mouse retina. J Neurosci. 2008; 28(19):4878-87. PMC: 3325486. DOI: 10.1523/JNEUROSCI.0828-08.2008. View