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Genes Dev ; 17(6): 738-47, 2003 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-12651892

RESUMO

The T-box transcription factor Tpit was identified as a cell-specific factor for expression of the pituitary proopiomelanocortin (POMC) gene. Expression of this factor is exclusively restricted to the pituitary POMC-expressing lineages, the corticotrophs and melanotrophs. We have now determined the role of this factor in pituitary cell differentiation. Tpit is a positive regulator for late POMC cell differentiation and POMC expression, but it is not essential for lineage commitment. The pituitary intermediate lobe normally contains only Tpit-expressing melanotrophs. Inactivation of the Tpit gene results in almost complete loss of POMC-expressing cells in this tissue, which now has a large number of gonadotrophs and a few clusters of Pit-1-independent thyrotrophs. The role of Tpit as a negative regulator of gonadotroph differentiation was confirmed in transgenic gain-of-function experiments. One mechanism to account for the negative role of Tpit in differentiation may be trans-repression between Tpit and the gonadotroph-restricted factor SF1. These data suggest that antagonism between Tpit and SF1 may play a role in establishment of POMC and gonadotroph lineages and that these lineages may arise from common precursors.


Assuntos
Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/fisiologia , Hipófise/embriologia , Fatores de Transcrição/genética , Fatores de Transcrição/fisiologia , Animais , Diferenciação Celular , Divisão Celular , Linhagem da Célula , Genótipo , Gonadotropinas/metabolismo , Imuno-Histoquímica , Óperon Lac , Luciferases/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Microscopia de Fluorescência , Modelos Biológicos , Mutagênese Sítio-Dirigida , Neurônios/metabolismo , Pró-Opiomelanocortina/metabolismo , Proteínas Recombinantes de Fusão/metabolismo , Recombinação Genética , Proteínas com Domínio T , Fatores de Tempo , Transfecção
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