Characterization of the spatio-temporal dynamics in thymic epithelial development

The work presented in this thesis is centered on the development and maturation of the epithelial compartment in the murine thymus and consequently its functional capacity to promote normal thymopoiesis. Two main aspects have been investigated in depth:
1. The role of the Dicer in thymic epithelial cell development and function
The endoribonuclease Dicer is critically required for the processing of most miRNA, a class of evolutionary conserved non-coding RNA that plays an important role in transcriptional regulation. The aim of the present study was to investigate the role of Dicer, and hence miRNA in general, in thymic epithelial cell development during embryogenesis and its function in maintaining thymopoiesis in the adult mouse. Specifically, I wished to investigate: A) the requirement of Dicer for TEC development, lineage specification and maintenance; B) the transcriptional changes upon a loss of Dicer expression targeted to the thymic epithelia and its consequences for thymic function; and C) the competence of T lymphocytes educated by a Dicer-deficient epithelial scaffold.
2. The capacity of β5t-expressing progenitor cells to form the cortical and medullar thymic epithelial compartments
Results obtained from a mouse experimental model that allows for conditional lineage tracing at early stages of thymic development suggested that most (if not all) thymic epithelial cells display hallmarks of having once adopted features characteristic of a cortical epithelial phenotype, i.e. the expression of the thymoproteasome subunit β5t. I extended these findings to probe: A) the precise timepoint of β5t expression during thymic epithelial development; B) the phenotype of β5t-expressing progenitor cells; C) the activity of β5t-expressing progenitor cells in later stages of thymus development; and D) the regenerative capacity of those cells in the post-natal thymus.
Taken together, these two research programs will provide unprecedented insight into the spatio-temporal dynamics of thymic epithelial cell development and function.