ArticleBrain structure & function2019
Two distinct GUCY2C circuits with PMV (hypothalamic) and SN/VTA (midbrain) origin.
Article in Brain structure & function, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Nutritionally Responsive PMv DAT Neurons Are Dynamically Regulated During Pubertal Transition.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Nutritionally responsive PMv DAT neurons are dynamically regulated during pubertal transition.bioRxiv : the preprint server for biology · 2025Article
- The ventral premammillary nucleus at the interface of environmental cues and social behaviors.Frontiers in neuroscience · 2025Review
- Immunotherapy for precision medicine in colorectal cancer.Expert review of precision medicine and drug development · 2025Article
- Brain-derived uroguanylin as a regulator of postprandial brown adipose tissue activation: a potential therapeutic approach for metabolic disorders.Frontiers in pharmacology · 2025Article
- Phosphodiesterase inhibition and Gucy2C activation enhance tyrosine hydroxylase Ser40 phosphorylation and improve 6-hydroxydopamine-induced motor deficits.Cell & bioscience · 2024Article
- GUCY2C signaling limits dopaminergic neuron vulnerability to toxic insults.NPJ Parkinson's disease · 2024Article
- Expression of guanylate cyclase C in human prefrontal cortex depends on sex and feeding status.Frontiers in molecular neuroscience · 2024Article
- Intestinal neuropod cell GUCY2C regulates visceral pain.The Journal of clinical investigation · 2023Article
- Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery.Frontiers in endocrinology · 2023Article
- Enteroendocrine cell regulation of the gut-brain axis.Frontiers in neuroscience · 2023Review
- Guanylyl cyclase C as a diagnostic and therapeutic target in colorectal cancer.Personalized medicine · 2022Review
- Role of uroguanylin's signalling pathway in the development of ischaemic stroke.The European journal of neuroscience · 2022Article
- Early Life Social Stress Causes Sex- and Region-Dependent Dopaminergic Changes that Are Prevented by Minocycline.Molecular neurobiology · 2022Article
- Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities.Frontiers in endocrinology · 2022Review
- From leptin to lasers: the past and present of mouse models of obesity.Expert opinion on drug discovery · 2021Article
- Emerging targets for the diagnosis of Parkinson's disease: examination of systemic biomarkers.Biomarkers in medicine · 2021Review
- Guanylyl cyclase 2C (GUCY2C) in gastrointestinal cancers: recent innovations and therapeutic potential.Expert opinion on therapeutic targets · 2021Review
- Guanylyl cyclase C as a biomarker for immunotherapies for the treatment of gastrointestinal malignancies.Biomarkers in medicine · 2021Review
- Tangential Intrahypothalamic Migration of the Mouse Ventral Premamillary Nucleus and Fgf8 Signaling.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Guanylyl cyclase C (GUCY2C) is the afferent central receptor in the gut-brain endocrine axis regulated by the anorexigenic intestinal hormone uroguanylin. GUCY2C mRNA and protein are produced in the hypothalamus, a major center regulating appetite and metabolic homeostasis. Further, GUCY2C mRNA and protein are expressed in the ventral midbrain, a principal structure regulating hedonic reward from behaviors including eating. While GUCY2C is expressed in hypothalamus and midbrain, its precise neuroanatomical organization and relationship with circuits regulating satiety remain unknown. Here, we reveal that hypothalamic GUCY2C mRNA is confined to the ventral premammillary nucleus (PMV), while in midbrain it is produced by neurons in the ventral tegmental area (VTA) and substantia nigra (SN). GUCY2C in the PMV is produced by 46% of neurons expressing anorexigenic leptin receptors, while in the VTA/SN it is produced in most tyrosine hydroxylase-immunoreactive neurons. In contrast to mRNA, GUCY2C protein is widely distributed throughout the brain in canonical sites of PMV and VTA/SN axonal projections. Selective stereotaxic ablation of PMV or VTA/SN neurons eliminated GUCY2C only in their respective canonical projection sites. Conversely, specific anterograde tracer analyses of PMV or VTA/SN neurons confirmed distinct GUCY2C-immunoreactive axons projecting to those canonical locations. Together, these findings reveal two discrete neuronal circuits expressing GUCY2C originating in the PMV in the hypothalamus and in the VTA/SN in midbrain, which separately project to other sites throughout the brain. They suggest a structural basis for a role for the GUCY2C-uroguanylin gut-brain endocrine axis in regulating homeostatic and behavioral components contributing to satiety.
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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.