Common properties of genetic networks supporting thymopoiesis in jawless and jawed vertebrates
All vertebrate adaptive immune systems exhibit distinct lymphocyte lineages. In jawless vertebrates, such as lampreys, T-like cells are thought to develop in lympho-epithelial structures at the tips of gill filaments, termed thymoids. However, it is unclear whether thymoids are functionally equivalent to the thymus of jawed vertebrates. Indeed, because the structural modules that are somatically assembled to form the antigen receptors of jawless and jawed vertebrates differ, development and selection of T cells may be governed by clade-specific genetic networks. To address this question, we have replaced the mouse Foxn1 gene, a key regulator of the thymic microenvironment in jawed vertebrates, with the orthologous FOXN1 lamprey gene, which is expressed in the thymoids alongside genes known to be targets of the mouse Foxn1 transcription factor. The reconstituted thymi are bi-potent, supporting normal T cell development, and, to a lesser extent, also fostering B cell development. The absence of overt autoimmunity in transgenic mice indicates that the lamprey FOXN1 gene can become an integral part of the thymic epithelial cell genetic network of the mouse. These findings highlight the remarkable similarity of thymic epithelial functions in jawed and jawless vertebrates, despite more than 500 million years of independent evolution. Our results thus suggest that the emergence of the Foxn1 transcription factor in the common ancestor of vertebrates was associated with the advent of a specialised tissue environment supporting the development and selection of T cells.