Hedgehog signaling controls thymocyte progenitor homeostasis and differentiation in the thymus
Hedgehog signaling controls thymocyte progenitor homeostasis and differentiation in the thymus
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DOI：
10.1038/ni1313
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发表时间：
2006-04-01
影响因子：
30.5
通讯作者：
Aifantis, I
中科院分区：
文献类型：
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作者：
El Abdaloussi, E;Graves, S;Aifantis, I
造血祖细胞向T细胞谱系的定型需要多种信号传导途径的整合。有证据表明，刺猬（Hh）信号通过其信号转导平滑（Smo）参与T细胞分化。然而，Hh通路的确切功能仍然存在争议，主要是因为尚未使用T细胞特异性体内遗传模型。使用前T细胞特异性、成熟T细胞特异性和poly（I）（.）poly（C）诱导Smo缺失和Smo信号拮抗剂，我们在这里报告Hh是T细胞祖细胞分化的重要正调节因子。此外，我们本地化Hh功能的前T细胞受体信号传导的一个阶段，连接Smo信号的Gli1和Gli2转录因子的活性，并证明Hh影响胸腺细胞的存活和增殖的调节。
Commitment of hematopoietic progenitors to the T cell lineage requires the integration of multiple signaling pathways. Evidence has suggested involvement of hedgehog (Hh) signaling in T cell differentiation through its signal transducer smoothened (Smo). However, the precise function of the Hh pathway remains controversial, mainly because T cell-specific in vivo genetic models have not been used. Using pre-T cell-specific, mature T cell-specific and poly( I)(.)poly(C)- inducible deletions of Smo and antagonists of Smo signaling, we report here that Hh is an essential positive regulator of T cell progenitor differentiation. Furthermore, we localize Hh function to a stage preceding pre-T cell receptor signaling, connect Smo signaling to the activity of the Gli1 and Gli2 transcription factors and demonstrate that Hh affects regulators of thymocyte survival and proliferation.