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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., Dos factores regulan el desarrollo del epitelio tímico, el factor de transcripción Foxn1 y las interacciones célula-célula entre timocitos y epitelio tímico, imprescindible a su vez para la maduración funcional de los timocitos. El trabajo re-evalúa el papel de ambos factores analizando comparativamente el desarrollo epitelial en timos sin Foxn1 ni timocitos (ratones nude), con Foxn1 pero sin timocitos (ratones NSG), con Foxn1 pero sin timocitos hasta después del nacimiento (ratones Ikaros-/-) y ratones WT con ambos factores durante todo el desarrollo. Los resultados confirman que el timo, como otras glándulas derivadas del endodermo, se desarrollan de acuerdo a un patrón de branching morphogenesis en el que la expresión de Foxn1 bloquea la formación del lumen de la glándula al tiempo que induce la diferenciación de genes epiteliales que culmina cuando la llegada de progenitores linfoides al primordio tímico induce la diferenciación de marcadores funcionales (MHC clase II, CD80, Aire)" Juan J. Muñoz, Esther Tobajas, Sonia Juara, Sara Montero, Agustín G. Zapata, Ministerio de Economía y Competitividad (MINECO), Depto. de Biología Celular, Fac. de Ciencias Biológicas, TRUE, pub

Numerous studies emphasize the relevance of thymocyte–thymic epithelial cell (TECs) interactions for the functional maturation of intrathymic T lymphocytes. The tyrosine kinase receptors, Ephs (erythropoietin-producing hepatocyte kinases) and their ligands, ephrins (Eph receptor interaction proteins), are molecules known to be involved in the regulation of numerous biological systems in which cell-to-cell interactions are particularly relevant. In the last years, we and other authors have demonstrated the importance of these molecules in the thymic functions and the T-cell development. In the present report, we review data on the effects of Ephs and ephrins in the functional maturation of both thymic epithelial microenvironment and thymocyte maturation as well as on their role in the lymphoid progenitor recruitment into the thymus., Ministerio de Economía y Competitividad (MINECO), Ministerio de Salud (España), Depto. de Biología Celular, Fac. de Ciencias Biológicas, TRUE, pub