Human semaphorin 3 variants link melanocortin ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
Human semaphorin 3 variants link melanocortin circuit development and energy balance
Author(s) :
Van Der Klaauw, Agatha A. [Auteur]
Croizier, Sophie [Auteur]
Mendes De Oliveira, Edson [Auteur]
Stadler, Lukas K. J. [Auteur]
Park, Soyoung [Auteur]
Kong, Youxin [Auteur]
Banton, Matthew C. [Auteur]
Tandon, Panna [Auteur]
Hendricks, Audrey E. [Auteur]
Keogh, Julia M. [Auteur]
Riley, Susanna E. [Auteur]
Papadia, Sofia [Auteur]
Henning, Elana [Auteur]
Bounds, Rebecca [Auteur]
Bochukova, Elena G. [Auteur]
Mistry, Vanisha [Auteur]
O''''rahilly, Stephen [Auteur]
Simerly, Richard B. [Auteur]
Minchin, James E. N. [Auteur]
Barroso, Ines [Auteur]
Jones, E. Yvonne [Auteur]
Bouret, Sebastien [Auteur]
Farooqi, I. Sadaf [Auteur]
Croizier, Sophie [Auteur]
Mendes De Oliveira, Edson [Auteur]
Stadler, Lukas K. J. [Auteur]
Park, Soyoung [Auteur]
Kong, Youxin [Auteur]
Banton, Matthew C. [Auteur]
Tandon, Panna [Auteur]
Hendricks, Audrey E. [Auteur]
Keogh, Julia M. [Auteur]
Riley, Susanna E. [Auteur]
Papadia, Sofia [Auteur]
Henning, Elana [Auteur]
Bounds, Rebecca [Auteur]
Bochukova, Elena G. [Auteur]
Mistry, Vanisha [Auteur]
O''''rahilly, Stephen [Auteur]
Simerly, Richard B. [Auteur]
Minchin, James E. N. [Auteur]
Barroso, Ines [Auteur]
Jones, E. Yvonne [Auteur]
Bouret, Sebastien [Auteur]

Farooqi, I. Sadaf [Auteur]
Journal title :
Cell
Abbreviated title :
Cell
Publication date :
2019-01-14
ISSN :
1097-4172
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Hypothalamic melanocortin neurons play a pivotal role in weight regulation. Here, we examined the contribution of Semaphorin 3 (SEMA3) signaling to the development of these circuits. In genetic studies, we found 40 rare ...
Show more >Hypothalamic melanocortin neurons play a pivotal role in weight regulation. Here, we examined the contribution of Semaphorin 3 (SEMA3) signaling to the development of these circuits. In genetic studies, we found 40 rare variants in SEMA3A-G and their receptors (PLXNA1-4; NRP1-2) in 573 severely obese individuals; variants disrupted secretion and/or signaling through multiple molecular mechanisms. Rare variants in this set of genes were significantly enriched in 982 severely obese cases compared to 4,449 controls. In a zebrafish mutagenesis screen, deletion of 7 genes in this pathway led to increased somatic growth and/or adiposity demonstrating that disruption of Semaphorin 3 signaling perturbs energy homeostasis. In mice, deletion of the Neuropilin-2 receptor in Pro-opiomelanocortin neurons disrupted their projections from the arcuate to the paraventricular nucleus, reduced energy expenditure, and caused weight gain. Cumulatively, these studies demonstrate that SEMA3-mediated signaling drives the development of hypothalamic melanocortin circuits involved in energy homeostasis.Show less >
Show more >Hypothalamic melanocortin neurons play a pivotal role in weight regulation. Here, we examined the contribution of Semaphorin 3 (SEMA3) signaling to the development of these circuits. In genetic studies, we found 40 rare variants in SEMA3A-G and their receptors (PLXNA1-4; NRP1-2) in 573 severely obese individuals; variants disrupted secretion and/or signaling through multiple molecular mechanisms. Rare variants in this set of genes were significantly enriched in 982 severely obese cases compared to 4,449 controls. In a zebrafish mutagenesis screen, deletion of 7 genes in this pathway led to increased somatic growth and/or adiposity demonstrating that disruption of Semaphorin 3 signaling perturbs energy homeostasis. In mice, deletion of the Neuropilin-2 receptor in Pro-opiomelanocortin neurons disrupted their projections from the arcuate to the paraventricular nucleus, reduced energy expenditure, and caused weight gain. Cumulatively, these studies demonstrate that SEMA3-mediated signaling drives the development of hypothalamic melanocortin circuits involved in energy homeostasis.Show less >
Language :
Anglais
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
CHU Lille
Inserm
Université de Lille
Inserm
Université de Lille
Collections :
Research team(s) :
Développement et plasticité du cerveau neuro-endocrine
Submission date :
2021-06-23T11:43:04Z