Mostrar el registro sencillo del ítem
dc.contributor.author
Nasif, Sofia
dc.contributor.author
Silva Junqueira de Souza, Flavio
dc.contributor.author
Gonzalez, Laura Elisabeth
dc.contributor.author
Yamashita, Miho
dc.contributor.author
Orquera, Daniela Paula
dc.contributor.author
Low, Malcolm J.
dc.contributor.author
Rubinstein, Marcelo
dc.date.available
2016-02-02T20:41:46Z
dc.date.issued
2015-04
dc.identifier.citation
Nasif, Sofia; Silva Junqueira de Souza, Flavio; Gonzalez, Laura Elisabeth; Yamashita, Miho; Orquera, Daniela Paula; et al.; Islet-1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 112; 15; 4-2015; E1861–E1870
dc.identifier.issn
0027-8424
dc.identifier.uri
http://hdl.handle.net/11336/3967
dc.description.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
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
National Academy of Sciences
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Pomc
dc.subject
Obesidad
dc.subject
Hipotálamo
dc.subject
Isl1
dc.subject.classification
Neurociencias
dc.subject.classification
Medicina Básica
dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
Islet-1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-03-30 10:35:44.97925-03
dc.journal.volume
112
dc.journal.number
15
dc.journal.pagination
E1861–E1870
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Washington
dc.description.fil
Fil: Nasif, Sofia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
dc.description.fil
Fil: Silva Junqueira de Souza, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina
dc.description.fil
Fil: Gonzalez, Laura Elisabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
dc.description.fil
Fil: Yamashita, Miho. University of Michigan. Department of Molecular and Integrative Physiology; Estados Unidos
dc.description.fil
Fil: Orquera, Daniela Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina
dc.description.fil
Fil: Low, Malcolm J.. University of Michigan. Department of Molecular and Integrative Physiology; Estados Unidos
dc.description.fil
Fil: Rubinstein, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. University of Michigan. Department of Molecular and Integrative Physiology; Estados Unidos
dc.journal.title
Proceedings of the National Academy of Sciences of The United States of America
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.pnas.org/content/112/15/E1861.long
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1073%2Fpnas.1500672112
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403183/
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/issn/0027-8424
Archivos asociados