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Nasif, S.; De Souza, F.S.J.; González, L.E.; Yamashita, M.; Orquera, D.P.; Low, M.J.; Rubinstein, M. "Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood" (2015) Proceedings of the National Academy of Sciences of the United States of America. 112(15):E1861-E1870
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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 DNAmotifs 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 transgenicmice 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. © 2015, National Academy of Sciences. All rights reserved.

Registro:

Documento: Artículo
Título:Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood
Autor:Nasif, S.; De Souza, F.S.J.; González, L.E.; Yamashita, M.; Orquera, D.P.; Low, M.J.; Rubinstein, M.
Filiación:Instituto de Investigaciones en Ingeniería Genética Y Biología Molecular, Consejo Nacional de Investigaciones Científicas Y Técnicas, 1428 Buenos Aires, Argentina
Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48105, United States
Palabras clave:Hypothalamus; Isl1; Melanocortin; Obesity; Pomc; beta tubulin; beta tubulin iii; calbindin 1; caspase 3; corticotropin; LIM homeodomain protein; lim homeodomain transcription factor islet 1; melanocortin; monoclonal antibody; neurogenin 3; neuropeptide; nPE1 protein; nPE2 protein; proopiomelanocortin; protein; tamoxifen; transcription factor; transcription factor Mash1; unclassified drug; insulin gene enhancer binding protein Isl-1; LIM homeodomain protein; proopiomelanocortin; protein binding; transcription factor; adult; adulthood; animal experiment; animal model; Article; binding affinity; binding site; body weight; brain region; cell differentiation; controlled study; DNA binding motif; embryo; embryo development; enhancer region; food intake; gene expression; gene mutation; human; hyperphagia; hypothalamus; immunocompetent cell; in vitro study; in vivo study; lifespan; mediobasal hypothalamus; nerve cell; nervous system development; nonhuman; obesity; ontogeny; pathophysiology; priority journal; protein binding; reporter gene; satiety; transactivation; transgenic zebrafish; zebra fish; animal; cytology; eating; embryology; female; fluorescence microscopy; gene expression regulation; gene silencing; genetics; hypothalamus; knockout mouse; male; metabolism; molecular genetics; nerve cell; nucleotide sequence; obesity; physiology; reverse transcription polymerase chain reaction; sequence homology; transgenic mouse; Danio rerio; Mus; Vertebrata; Adiposity; Animals; Base Sequence; Cell Differentiation; Eating; Female; Gene Expression Regulation, Developmental; Gene Knockdown Techniques; Hyperphagia; Hypothalamus; LIM-Homeodomain Proteins; Male; Mice, Knockout; Mice, Transgenic; Microscopy, Fluorescence; Molecular Sequence Data; Neurons; Obesity; Pro-Opiomelanocortin; Protein Binding; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Nucleic Acid; Transcription Factors; Zebrafish
Año:2015
Volumen:112
Número:15
Página de inicio:E1861
Página de fin:E1870
DOI: http://dx.doi.org/10.1073/pnas.1500672112
Título revista:Proceedings of the National Academy of Sciences of the United States of America
Título revista abreviado:Proc. Natl. Acad. Sci. U. S. A.
ISSN:00278424
CODEN:PNASA
CAS:beta tubulin, 87090-36-6; caspase 3, 169592-56-7; corticotropin, 11136-52-0, 9002-60-2, 9061-27-2; proopiomelanocortin, 66796-54-1; protein, 67254-75-5; tamoxifen, 10540-29-1; insulin gene enhancer binding protein Isl-1; LIM-Homeodomain Proteins; Pro-Opiomelanocortin; Transcription Factors
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00278424_v112_n15_pE1861_Nasif

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Citas:

---------- APA ----------
Nasif, S., De Souza, F.S.J., González, L.E., Yamashita, M., Orquera, D.P., Low, M.J. & Rubinstein, M. (2015) . Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood. Proceedings of the National Academy of Sciences of the United States of America, 112(15), E1861-E1870.
http://dx.doi.org/10.1073/pnas.1500672112
---------- CHICAGO ----------
Nasif, S., De Souza, F.S.J., González, L.E., Yamashita, M., Orquera, D.P., Low, M.J., et al. "Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood" . Proceedings of the National Academy of Sciences of the United States of America 112, no. 15 (2015) : E1861-E1870.
http://dx.doi.org/10.1073/pnas.1500672112
---------- MLA ----------
Nasif, S., De Souza, F.S.J., González, L.E., Yamashita, M., Orquera, D.P., Low, M.J., et al. "Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood" . Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 15, 2015, pp. E1861-E1870.
http://dx.doi.org/10.1073/pnas.1500672112
---------- VANCOUVER ----------
Nasif, S., De Souza, F.S.J., González, L.E., Yamashita, M., Orquera, D.P., Low, M.J., et al. Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood. Proc. Natl. Acad. Sci. U. S. A. 2015;112(15):E1861-E1870.
http://dx.doi.org/10.1073/pnas.1500672112