Tpit determines alternate fates during pituitary cell differentiation.
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.
Pulichino
Anne-Marie
AM
Laboratoire de Génétique moléculaire, Institut de recherches cliniques de Montréal (IRCM), Montréal, Quebec, Canada H2W 1R7.
Vallette-Kasic
Sophie
S
Tsai
Judy Peih-Ying
JP
Couture
Catherine
C
Gauthier
Yves
Y
Drouin
Jacques
J
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D019070:Cell Lineage; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006062:Gonadotropins / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000502:physiology*; D007150:Immunohistochemistry; D007763:Lac Operon; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000378:metabolism; D010902:Pituitary Gland / Q000196:embryology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D011995:Recombination, Genetic; D020825:T-Box Domain Proteins; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology*; D014162:Transfection
D006062:Gonadotropins; D018398:Homeodomain Proteins; D011993:Recombinant Fusion Proteins; D020825:T-Box Domain Proteins; C424031:Tbx19 protein, mouse; D014157:Transcription Factors; D011333:Pro-Opiomelanocortin; D008156:Luciferases