Functional identity of hypothalamic melanocortin neurons depends on Tbx3.

Nature Metabolism
Carmelo QuartaMatthias H Tschöp

Abstract

Heterogeneous populations of hypothalamic neurons orchestrate energy balance via the release of specific signatures of neuropeptides. However, how specific intracellular machinery controls peptidergic identities and function of individual hypothalamic neurons remains largely unknown. The transcription factor T-box 3 (Tbx3) is expressed in hypothalamic neurons sensing and governing energy status, whereas human TBX3 haploinsufficiency has been linked with obesity. Here, we demonstrate that loss of Tbx3 function in hypothalamic neurons causes weight gain and other metabolic disturbances by disrupting both the peptidergic identity and plasticity of Pomc/Cart and Agrp/Npy neurons. These alterations are observed after loss of Tbx3 in both immature hypothalamic neurons and terminally differentiated mouse neurons. We further establish the importance of Tbx3 for body weight regulation in Drosophila melanogaster and show that TBX3 is implicated in the differentiation of human embryonic stem cells into hypothalamic Pomc neurons. Our data indicate that Tbx3 directs the terminal specification of neurons as functional components of the melanocortin system and is required for maintaining their peptidergic identity. In summary, we report the d...Continue Reading

References

Sep 1, 1987·Clinical Genetics·A SchinzelA Prader
Apr 9, 1999·Nature Neuroscience·T M HahnM W Schwartz
Oct 25, 2001·Proceedings of the National Academy of Sciences of the United States of America·T OsterwalderH Keshishian
Feb 13, 2002·International Journal of Obesity and Related Metabolic Disorders : Journal of the International Association for the Study of Obesity·G J Morton, M W Schwartz
Jul 3, 2002·Genome Biology·Val Wilson, Frank L Conlon
Mar 27, 2004·Endocrinology·Sebastien G Bouret, Richard B Simerly
Apr 28, 2005·Nature Neuroscience·Roger D Cone
Feb 14, 2007·Developmental Dynamics : an Official Publication of the American Association of Anatomists·T Quinn Crawford, Henk Roelink
Sep 18, 2007·Genesis : the Journal of Genetics and Development·Mandar Deepak MuzumdarLiqun Luo
Sep 22, 2007·The Journal of Clinical Investigation·Ruben NogueirasMatthias H Tschöp
Oct 3, 2007·PLoS Genetics·Jeffrey T Leek, John D Storey
Jan 4, 2008·Mechanisms of Development·Jie ShenGert O Pflugfelder
Jun 7, 2008·Gene Expression Patterns : GEP·Marco PontecorviNicoletta Kessaris
Jan 23, 2009·Nature Neuroscience·Qingchun TongBradford B Lowell
Apr 10, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anthony N van den PolChristian Broberger
Sep 22, 2009·Brain Research·Krister S Eriksson, Emmanuel Mignot
Nov 26, 2009·American Journal of Medical Genetics. Part a·Helen LindenUsha Kini
Oct 12, 2010·Nature Methods·Sourav BandyopadhyayTrey Ideker
Jan 25, 2011·Journal of Proteome Research·Jürgen CoxMatthias Mann
Sep 21, 2011·PloS One·Anja HildebrandtRonald P Kühnlein
Dec 30, 2011·Nature Methods·Matthias H TschöpEric Ravussin
Mar 30, 2012·Omics : a Journal of Integrative Biology·Guangchuang YuQing-Yu He
Nov 28, 2012·Cell·Zachary A KnightJeffrey M Friedman
Feb 22, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Cheng ZhanMinmin Luo
Mar 23, 2013·Fly·Lisa R MayerGert O Pflugfelder
Apr 2, 2013·Frontiers in Endocrinology·Berengere Coupe, Sebastien G Bouret
Apr 27, 2013·Science·Davide DulcisNicholas C Spitzer
Nov 16, 2013·Trends in Endocrinology and Metabolism : TEM·Lígia Sousa-FerreiraCláudia Cavadas
Dec 10, 2013·Stem Cell Reports·Clair E WeidgangAlexander Kleger
May 21, 2014·Nature Reviews. Neuroscience·Gregory J MortonMichael W Schwartz

❮ Previous
Next ❯

Citations

Feb 1, 2019·Nature Metabolism·Arnaud Obri, Marc Claret
Nov 2, 2019·Gene·Saif F KhanSharon Prince
Feb 27, 2021·Nature Metabolism·Carmelo QuartaDaniela Cota

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE90806
GSE93374

Methods Mentioned

BETA
affinity
targeted knock-in
transgenic
RNA-seq
single-cell sequencing
immunoprecipitation
PCR
nuclear magnetic resonance
transfection
Assay

Software Mentioned

HTseq
R package sva
GraphPad Prism
Perseus
Image studio
- count
Andromeda
GeneSwitch
Light
R

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.