Tpit determines alternate fates during pituitary cell differentiation
Abstract
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.
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Footnotes
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↵1 Corresponding author.
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E-MAIL drouinj{at}ircm.qc.ca; FAX (514)987-5575.
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Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1065703.
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- Received December 9, 2002.
- Accepted January 27, 2003.
- Cold Spring Harbor Laboratory Press