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.

中文翻译：

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FoxN1通过修改基于上皮微管发生的发育模式来介导胸腺皮质-髓质的分化。

确定胸腺上皮前体对两个主要的胸腺上皮细胞谱系cTECs和mTECs的承诺的机制仍然未知。在这里我们显示，FoxN1 nu突变消除了胸腺上皮细胞的分化，根据典型的分支形态发生和微管发生发展模式，导致管状分支结构的形成。在FoxN1的存在下，在无淋巴结样的NSG和胎儿的Ikaros-/-胸腺中，没有管腔形成，仅部分根尖分化。这启动了皮层髓质分化，诱导了顶叶分化细胞中髓质基因的表达和非顶叶分化细胞中皮质基因的表达，这肯定会在wt和出生后的Ikaros-/-小鼠中分化。所以，