Cells encounter numerous signals during the development of an organism that induce division, differentiation, and apoptosis. These signals need to be present for defined intervals in order to induce stable changes in the cellular phenotype. The point after which an inducing signal is no longer needed for completion of a differentiation program can be termed the "commitment point." Meiotic development in the yeast Saccharomyces cerevisiae (sporulation) provides a model system to study commitment. Similar to differentiation programs in multicellular organisms, the sporulation program in yeast is regulated by a transcriptional cascade that produces early, middle, and late sets of sporulation-specific transcripts. Although critical meiosis-specific events occur as early genes are expressed, commitment does not take place until middle genes are induced. Middle promoters are activated by the Ndt80 transcription factor, which is produced and activated shortly before most middle genes are expressed. In this article, I discuss the connection between Ndt80 and meiotic commitment. A transcriptional regulatory pathway makes NDT80 transcription contingent on the prior expression of early genes. Once Ndt80 is produced, the recombination (pachytene) checkpoint prevents activation of the Ndt80 protein. Upon activation, Ndt80 triggers a positive autoregulatory loop that leads to the induction of genes that promote exit from prophase, the meiotic divisions, and spore formation. The pathway is controlled by multiple feed-forward loops that give switch-like properties to the commitment transition. The conservation of regulatory components of the meiotic commitment pathway and the recently reported ability of Ndt80 to increase replicative life span are discussed.

• PMID: 22390969
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Journal Article | Research Support, N.I.H., Extramural | Research Support, U.S. Gov't, Non-P.H.S. | Review

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Winter E

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