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Publication : FoxN1 mediates thymic cortex-medulla differentiation through modifying a developmental pattern based on epithelial tubulogenesis.

First Author  Muñoz JJ Year  2019
Journal  Histochem Cell Biol Volume  152
Issue  6 Pages  397-413
PubMed ID  31552487 Mgi Jnum  J:293206
Mgi Id  MGI:6452323 Doi  10.1007/s00418-019-01818-z
Citation  Munoz JJ, et al. (2019) FoxN1 mediates thymic cortex-medulla differentiation through modifying a developmental pattern based on epithelial tubulogenesis. Histochem Cell Biol 152(6):397-413
abstractText  The mechanisms that determine the commitment of thymic epithelial precursors to the two major thymic epithelial cell lineages, cTECs and mTECs, remain unknown. Here we show that FoxN1 nu mutation, which abolishes thymic epithelium differentiation, results in the formation of a tubular branched structure according to a typical branching morphogenesis and tubulogenesis developmental pattern. In the presence of FoxN1, in alymphoid NSG and fetal Ikaros-/- thymi, there is no lumen formation and only partial apical differentiation. This initiates cortex-medulla differentiation inducing expression of medullary genes in the apically differentiating cells and of cortical genes in the non-apically differentiating cells, which will definitely differentiate in wt and postnatal Ikaros-/- mice. Therefore, the thymus development is based on a branching morphogenesis and tubulogenesis developmental pattern: FoxN1 expression in the thymic primordium inhibits tubulogenesis and induces the expression of genes involved in TEC differentiation, which culminates with the expression of functional cell markers, i.e., MHCII, CD80, Aire in both postnatal Ikaros-/- and WT thymi after arrival of lymphoid progenitor cells.
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