ArticleProceedings of the National Academy of Sciences of the United States of America2015
Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 80 citations in OpenAlex.
- Two parallel neural ectoderm progenitors contribute to the developing brain.Nature neuroscience · 2026Article
- Scalable hypothalamic neuron differentiation from human pluripotent stem cells suitable for modeling metabolic disorders.Stem cell reports · 2026Article
- POMC neuron METTL14/mNature communications · 2026Article
- Highly Conserved STAT3 Motifs Present in the Neuronal Pomc Enhancer nPE1 are Critical for Maximal Hypothalamic Pomc Expression.Molecular neurobiology · 2025Article
- Reduced Availability of Essential Amino Acids Disrupts Differentiation of Anorexigenic POMC Neurons in the Fetal Rat Hypothalamus.Molecular neurobiology · 2025Article
- Neuronal activation in the axolotl brain promotes tail regeneration.NPJ Regenerative medicine · 2025Article
- Control of tuberal hypothalamic development and its implications in metabolic disorders.Nature reviews. Endocrinology · 2025Review
- Identification of ThreeAnimals : an open access journal from MDPI · 2024Article
- Regulation of neuronal fate specification and connectivity of the thalamic reticular nucleus by the Ascl1-Isl1 transcriptional cascade.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- 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
- Arcuate Nucleus of the Hypothalamus: Anatomy, Physiology, and Diseases.Experimental neurobiology · 2023Review
- AgRP Neuron-Specific Ablation Represses Appetite, Energy Intake, and Somatic Growth in Larval Zebrafish.Biomedicines · 2023Article
- TheFrontiers in endocrinology · 2023Article
- Zebrafish as a model to investigate the CRH axis and interactions with DISC1.Current opinion in endocrine and metabolic research · 2022Review
- Ontogenetic rules for the molecular diversification of hypothalamic neurons.Nature reviews. Neuroscience · 2022Review
- Molecular profile and response to energy deficit of leptin-receptor neurons in the lateral hypothalamus.Scientific reports · 2022Article
- Formation of the Mouse Internal Capsule and Cerebral Peduncle: A Pioneering Role for Striatonigral Axons as Revealed inThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Food intake and body weight regulation depend on proper expression of the proopiomelanocortin gene (Pomc) in a group of neurons located in the mediobasal hypothalamus of all vertebrates. These neurons release POMC-encoded melanocortins, which are potent anorexigenic neuropeptides, and their absence from mice or humans leads to hyperphagia and severe obesity. Although the pathophysiology of hypothalamic POMC neurons is well understood, the genetic program that establishes the neuronal melanocortinergic phenotype and maintains a fully functional neuronal POMC phenotype throughout adulthood remains unknown. Here, we report that the early expression of the LIM-homeodomain transcription factor Islet 1 (ISL1) in the developing hypothalamus promotes the terminal differentiation of melanocortinergic neurons and is essential for hypothalamic Pomc expression since its initial onset and throughout the entire lifetime. We detected ISL1 in the prospective hypothalamus just before the onset of Pomc expression and, from then on, Pomc and Isl1 coexpress. ISL1 binds in vitro and in vivo to critical homeodomain binding DNA motifs present in the neuronal Pomc enhancers nPE1 and nPE2, and mutations of these sites completely disrupt the ability of these enhancers to drive reporter gene expression to hypothalamic POMC neurons in transgenic mice and zebrafish. ISL1 is necessary for hypothalamic Pomc expression during mouse and zebrafish embryogenesis. Furthermore, conditional Isl1 inactivation from POMC neurons impairs Pomc expression, leading to hyperphagia and obesity. Our results demonstrate that ISL1 specifies the identity of hypothalamic melanocortin neurons and is required for melanocortin-induced satiety and normal adiposity throughout the entire lifespan.
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