Thymus development and function
Macroscopic view of an embryonic mouse thymus. The fluorescence originates from the epithelial compartment.
What clues does the thymus have to offer?
The thymus is a primary lymphoid organ whose function is to provide mature and self-tolerant T lymphocytes that are required to fight infection and maintain tissue integrity. The thymus is a unique evolutionary innovation of vertebrates and thus lends itself to both phylogenetic and ontogenetic analyses of a broad range of model organisms and the full complement of modern genetic and cell biological approaches.
Thymus and T cell development in the mouse
Thymopoiesis depends on the provision of a dedicated epithelial microenvironment that attracts, maintains, and specifies T cell progenitors and supports their differentiation into mature, self-tolerant T cells. We are interested in the molecular basis of thymic epithelial development and the characterization of the epithelial progenitor cell. To this end, we interfere with the function of various signalling pathways, such as BMP, Wnt, Fgf, etc. in thymic epithelial cells in vivo in order to study their roles in the regulation of TEC specification, proliferation and differentiation. We have previously shown that the function of the stromal niche required for the attraction and specification of lymphoid progenitor cells depends on the Foxn1 transcription factor. We rebuild this niche function in vivo in transgenic mice nullizygous for Foxn1 by re-expression of individual target genes of the Foxn1 transcription factor, singly or in combination. Ultimately, we wish to use this information to be able to engineer artificial thymus stroma at ectopic sites as a potential means to counter the ill-effects of diseased thymic tissue.