FoxN1 mediates thymic cortex–medulla differentiation through modifying a developmental pattern based on epithelial tubulogenesis

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Muñoz, Juan José and Tobajas, Esther and Juara, Sonia and Montero Herradón, Sara and Zapata González, Agustín Gregorio (2019) FoxN1 mediates thymic cortex–medulla differentiation through modifying a developmental pattern based on epithelial tubulogenesis. Histochemistry and Cell Biology, 152 . pp. 397-413. ISSN 1432-119X

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Official URL: https://link.springer.com/article/10.1007/s00418-019-01818-z



Abstract

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.

Resumen (otros idiomas)

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

Item Type:Article
Uncontrolled Keywords:Thymus, branching morphogenesis, tubulogenesis, thymic epithelium, FoxN1
Subjects:Medical sciences > Biology > Cytology
ID Code:60951
Deposited On:15 Jun 2020 20:09
Last Modified:24 Mar 2021 11:26

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