Wnt signalling pathways have been reported to be involved in thymus development but their precise role in the development of both thymic epithelium (TE) and thymocytes is controversial. Herein, we examined embryonic, postnatal and adult thymi of mice with a specific deletion of β-catenin gene in FoxN1⁺ thymic epithelial cells (TECs). Together with a high postnatal mouse mortality, the analysis showed severe thymic hypocellularity, largely due an important reduction in numbers of developing thymocytes, and delayed, partially blocked maturation of mutant TECs. Affected TECs included largely cortical (c) TEC subsets, such as immature MTS20⁺ TECs, Ly51⁺ cTECs and a remarkable, rare Ly51⁺MTS20⁺MHCII^hi cell subpopulation previously reported to contain thymic epithelial progenitor cells (TEPCs) (Ulyanchenko et al., Cell Rep 14:2819–2832, 2016). In addition, altered postnatal organization of mutant thymic medulla failed to organize a unique, central epithelial area. This delayed maturation of TE cell components correlated with low transcript production of some molecules reported to be masters for TEC maturation, such as EphB2, EphB3 and RANK. Changes in the thymic lymphoid component became particularly evident after birth, when molecules expressed by TECs and involved in early T-cell maturation, such as CCL25, CXCL12 and Dll4, exhibited minimal values. This represented a partial blockade of the progression of DN to DP cells and reduced proportions of this last thymocyte subset. At 1 month, in correlation with a significant increase in transcript production, the DP cell percentage increased in correlation with a significant fall in the number of mature TCRαβ^hi thymocytes and peripheral T lymphocytes.

据报道，Wnt 信号通路参与胸腺发育，但它们在胸腺上皮 (TE) 和胸腺细胞发育中的确切作用是有争议的。在这里，我们检查了 FoxN1 ⁺胸腺上皮细胞 (TECs) 中 β- 连环蛋白基因特异性缺失的小鼠的胚胎、出生后和成年胸腺。加上高出生后小鼠死亡率，分析显示严重的胸腺细胞减少，主要是由于发育中的胸腺细胞数量显着减少，以及突变 TECs 的成熟延迟、部分受阻。受影响的 TECs 主要包括皮质 (c) TEC 亚群，例如未成熟的 MTS20 ⁺ TECs、Ly51 ⁺ cTECs 和显着的罕见 Ly51 ⁺ MTS20 ⁺ MHCII^你好先前报道的细胞亚群含有胸腺上皮祖细胞 (TEPC) (Ulyanchenko et al., Cell Rep 14:2819–2832, 2016)。此外，突变胸腺髓质的改变的产后组织未能组织一个独特的中央上皮区域。TE 细胞成分的这种延迟成熟与据报道是 TEC 成熟的主要分子（例如 EphB2、EphB3 和 RANK）的低转录产物产生相关。胸腺淋巴成分的变化在出生后变得特别明显，当由 TECs 表达并参与早期 T 细胞成熟的分子（如 CCL25、CXCL12 和 Dll4）表现出最小值时。这代表了 DN 向 DP 细胞进展的部分阻断，并降低了最后一个胸腺细胞亚群的比例。1个月时，^hi胸腺细胞和外周 T 淋巴细胞。