ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2012) 29 S56.3

Transcriptional and epigenetic mechanisms for cell fate choice in pituitary

J. Drouin

Institut de recherches cliniques de Montréal (IRCM), Montréal, Quebec, Canada.

All secretory cells of the anterior and intermediate pituitary derive from the oral ectoderm that forms Rathke’s pouch. Pituitary progenitors present in the pouch as well as similar progenitor/stem cells that remain along the cleft of the adult gland, are marked by expression of Sox2. Sox2-positive progenitors can self-replicate or enter differentiation. Before any differentiation marker is expressed, progenitors first exit the cell cycle under the control of the cell cycle inhibitor p57kip2; this mechanism appears to be restricted to progenitors and the related p27kip1 prevents cell cycle re-entry of differentiated cells. Initial events involved in differentiation and determination of cell fate are still poorly understood but transcriptional regulators driving terminal differentiation of pituitary lineages have been identified. Thus, Pit1 is required for terminal differentiation of somatotropes, lactotropes and thyrotropes whereas SF1 is required to complete differentiation of gonadotropes. Similarly, we identified Tpit as the transcriptional regulator for terminal differentiation of both POMC-expressing lineages, the corticotropes and melanotropes. The requirement on the same factor Tpit for terminal differentiation of both lineages does not explain the cell fate choice between these lineages. The combinatorial action of other transcription factors together with Tpit is one model that may direct unique cell fate choices. Interestingly, we have identified a factor that is expressed slightly before Tpit, only in melanotropes and that behaves as a cell fate switch and selector gene since its knockout results in a switch from melanotrope to corticotrope identify. Current evidence suggests that epigenetic changes including chromatin remodeling are required in order to change the outcome of Tpit-driven gene expression and cell identity. Genome-wide alteration of chromatin organization thus sets the stage for transcriptionnally driven terminal differentiation.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details are unavailable.

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