Maintenance of Thymic Epithelial Phenotype Requires Extrinsic Signals in Mouse and Zebrafish

Abstract

Thymopoiesis strictly depends on proper differentiation of the thymic epithelial anlage. Differentiation of thymic epithelial cells (TECs) is controlled by the Foxn1 transcription factor. The in vivo signals initiating and maintaining Foxn1 expression in the future thymus anlage are unknown. In the mouse, bone morphogenetic protein (BMP) signaling is required for the maintenance of Foxn1 expression in TECs, as shown here by lineage tracing using a Foxn1-driven Cre transgene. Loss of Foxn1 expression after BMP inhibition reverts TECs to a basal state of pharyngeal epithelium unable to support T cell development; it does not divert them into a parathyroid fate. In zebrafish larvae, BMP inhibition likewise causes loss of foxn1 expression in the thymic anlage and subsequent impairment of thymopoiesis. These results indicate an evolutionarily conserved role of BMP signaling in the maintenance of Foxn1 expression.