Evolution of thymopoietic microenvironments

<jats:p> In vertebrates, the development of lymphocytes from undifferentiated haematopoietic precursors takes place in so-called primary lymphoid organs, such as the thymus. Therein, lymphocytes undergo a complex differentiation and selection process that culminates in the generation of a pool of mature T cells that collectively express a self-tolerant repertoire of somatically diversified antigen receptors. Throughout this entire process, the microenvironment of the thymus in large parts dictates the sequence and outcome of the lymphopoietic activity. In vertebrates, direct genetic evidence in some species and circumstantial evidence in others suggest that the formation of a functional thymic microenvironment is controlled by members of the Foxn1/4 family of transcription factors. In teleost fishes, both <jats:italic>Foxn1</jats:italic> and <jats:italic>Foxn4</jats:italic> contribute to thymopoietic activity, whereas <jats:italic>Foxn1</jats:italic> is both necessary and sufficient in the mammalian thymus. The evolutionary history of <jats:italic>Foxn1/4</jats:italic> genes suggests that an ancient <jats:italic>Foxn4</jats:italic> gene lineage gave rise to the <jats:italic>Foxn1</jats:italic> genes in early vertebrates, raising the question of the thymopoietic capacity of the ancestor common to all vertebrates. Recent attempts to reconstruct the early events in the evolution of thymopoietic tissues by replacement of the mouse <jats:italic>Foxn1</jats:italic> gene by <jats:italic>Foxn1</jats:italic> -like genes isolated from various chordate species suggest a plausible scenario. It appears that the primordial thymus was a bi-potent lymphoid organ, supporting both B cell and T cell development; however, during the course of vertebrate, evolution B cell development was gradually diminished converting the thymus into a site specialized in T cell development. </jats:p>