The essence of a developmental decision is to convert a temporary difference between two cells, for example in their current exposure to environmental signals, into a long-term, irreversible difference in phenotype and function. For years, one of the most striking examples of this mechanism has been the choice of developing T cells between maturation in the CD4+ CD8- lineages or the CD4- CD8+ lineages, but the molecular mechanisms underpinning this decision have remained poorly understood. Three elegant studies published recently in Nature Immunology establish a sophisticated hierarchy of transcriptional regulators in which expression of triggering factors is followed by expression of enforcement factors, including Thpok and Runx3, to determine CD4/CD8-lineage choice.
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Ellen V. Rothenberg (2008) studied this question.
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