ArticleNature metabolism2019
Functional identity of hypothalamic melanocortin neurons depends on Tbx3.
Article in Nature metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- IMPROVE 2025: The 3rd International Meeting on Pathway-Related Obesity: Vision & Evidence.Clinical obesity · 2026Article
- Scalable hypothalamic neuron differentiation from human pluripotent stem cells suitable for modeling metabolic disorders.Stem cell reports · 2026Article
- Review
- Hypothalamic control of puberty: from neuronal circuits to mechanisms for its metabolic regulation.Reviews in endocrine & metabolic disorders · 2026Review
- Beyond satiety: unraveling the complex roles of POMC neurons in behavior and metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- POMC neuron METTL14/mNature communications · 2026Article
- Reduced Availability of Essential Amino Acids Disrupts Differentiation of Anorexigenic POMC Neurons in the Fetal Rat Hypothalamus.Molecular neurobiology · 2025Article
- The expanding landscape of genetic causes of obesity.Pediatric research · 2025Review
- Control of tuberal hypothalamic development and its implications in metabolic disorders.Nature reviews. Endocrinology · 2025Review
- Liver-innervating vagal sensory neurons are indispensable for the development of hepatic steatosis and anxiety-like behavior in diet-induced obese mice.Nature communications · 2025Article
- Transcriptomic profiling of murine GnRH neurons reveals developmental trajectories linked to human reproduction and infertility.Theranostics · 2025Article
- Traditional Chinese Medicine Treats Obesity by Regulating the Central Nervous System via Short-chain Fatty Acids.Current pharmaceutical design · 2025Review
- Updates on Rare Genetic Variants, Genetic Testing, and Gene Therapy in Individuals With Obesity.Current obesity reports · 2024Review
- The homeodomain transcription factor Six3 regulates hypothalamic Pomc expression and its absence from POMC neurons induces hyperphagia and mild obesity in male mice.Molecular metabolism · 2024Article
- A mammalian tripartite enhancer cluster controls hypothalamicProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Single cell tracing of Pomc neurons reveals recruitment of 'Ghost' subtypes with atypical identity in a mouse model of obesity.Nature communications · 2024Article
- Loss of Tbx3 in Mouse Eye Causes Retinal Angiogenesis Defects Reminiscent of Human Disease.Investigative ophthalmology & visual science · 2023Article
- TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration.BMC biology · 2023Article
- Hierarchical deployment of Tbx3 dictates the identity of hypothalamic KNDy neurons to control puberty onset.Science advances · 2022Article
- Ontogenetic rules for the molecular diversification of hypothalamic neurons.Nature reviews. Neuroscience · 2022Review
Corrections and comments
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Authors and funding
31 authors at 10 institutions in 4 countries.
Funding
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 discovery of a key mechanistic process underlying the functional heterogeneity of hypothalamic neurons governing body weight and systemic metabolism.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.